Activin receptor-like kinase 1(ALK1)is a transmembrane serine/threonine receptor kinase of the transforming growth factor beta(TGFβ)receptor superfamily.ALK1 is specifically expressed in vascular endothelial cells,an...Activin receptor-like kinase 1(ALK1)is a transmembrane serine/threonine receptor kinase of the transforming growth factor beta(TGFβ)receptor superfamily.ALK1 is specifically expressed in vascular endothelial cells,and its dynamic changes are closely related to the proliferation of endothelial cells,the recruitment of pericytes to blood vessels,and functional differentiation during embryonic vascular development.The pathophysiology of many cerebrovascular diseases is today understood as a disorder of endothelial cell function and an imbalance in the proportion of vascular cells.Indeed,mutations in ALK1 and its co-receptor endoglin are major genetic risk factors for vascular arteriovenous malformation.Many studies have shown that ALK1 is closely related to the development of cerebral aneurysms,arteriovenous malformations,and cerebral atherosclerosis.In this review,we describe the various roles of ALK1 in the regulation of angiogenesis and in the maintenance of cerebral vascular homeostasis,and we discuss its relationship to functional dysregulation in cerebrovascular diseases.This review should provide new perspectives for basic research on cerebrovascular diseases and offer more effective targets and strategies for clinical diagnosis,treatment,and prevention.展开更多
Secondary vascular development is a key biological characteristic of woody plants and the basis of wood formation.Our understanding of gene expression regulation and dynamic changes in microRNAs(miRNAs)during secondar...Secondary vascular development is a key biological characteristic of woody plants and the basis of wood formation.Our understanding of gene expression regulation and dynamic changes in microRNAs(miRNAs)during secondary vascular development is still limited.Here we present an integrated analysis of the miRNA and mRNA transcriptome of six phase-specific tissues-the shoot apex,procambium,primary vascular tissue,cambium,secondary phloem,and secondary xylem-in Populus tomentosa.Several novel regulatory modules,including the PtoTCP20-miR396d-PtoGRF15 module,were identified during secondary vascular development in Populus.A series of biochemical and molecular experiments confirmed that PtoTCP20 activated transcription of the miR396d precursor gene and that miR396d targeted PtoGRF15 to downregulate its expression.Plants overexpressing miR396d(35S:miR396d)showed enhanced secondary growth and increased xylem production.Conversely,during the transition from primary to secondary vascular development,plants with downregulated PtoTCP20expression(PtoTCP20-SRDX),downregulated miR396 expression(35S:STTM396),and PtoGRF15 overexpression(35S:PtoGRF15)showed delayed secondary growth.Novel regulatory modules were identified by integrated analysis of the miRNA and mRNA transcriptome,and the regulatory role of the PtoTCP20-miR396d-PtoGRF15 signaling cascade in secondary vascular development was validated in Populus,providing information to support improvements in forest cultivation and wood properties.展开更多
Background: Hypertension, also known as increased blood pressure, is a phenomenon in which blood flows in blood vessels and causes persistently higher-than-normal pressure on the vessel wall. The identification of nov...Background: Hypertension, also known as increased blood pressure, is a phenomenon in which blood flows in blood vessels and causes persistently higher-than-normal pressure on the vessel wall. The identification of novel prognostic and pathogenesis biomarkers plays a key role in the management of hypertension. Methods: The GSE7483 and GSE75815 datasets from the gene expression omnibus (GEO) database were used to identify the genes associated with hypertension that were differentially expressed genes (DEGs). The functional role of the DEGs was elucidated by gene body (GO) enrichment analysis. In addition, we performed an immune infiltration assay and GSEA on the DEGs of hypertensive patients and verified the expression of novel DEGs in the blood of hypertensive patients by RT-qPCR. Results: A total of 267 DEGs were identified from the GEO database. GO analysis revealed that these genes were associated mainly with biological processes such as fibroblast proliferation, cell structural organization, extracellular matrix organization, vasculature development regulation, and angiogenesis. We identified five possible biomarkers, Ecm1, Sparc, Sphk1, Thbsl, and Mecp2, which correlate with vascular development and angiogenesis characteristic of hypertension by bioinformatics, and explored the clinical expression levels of these genes by RT-qPCR, and found that Sparc, Sphk1, and Thbs1 showed significant up-regulation, in agreement with the results of the bioinformatics analysis. Conclusion: Our study suggested that Sparc, Sphk1 and Thbs1 may be potential novel biomarkers for the diagnosis, treatment and prognosis of hypertension and that they are involved in the regulation of vascular development and angiogenesis in hypertension.展开更多
In Arabidopsis, the CLAVATA3/EMBRYO SURROUNDING REGION-RELATED (CLE) peptides play important roles in regulating proliferation and differentiation of plant-specific stem cells. Although receptors of CLEs are reporte...In Arabidopsis, the CLAVATA3/EMBRYO SURROUNDING REGION-RELATED (CLE) peptides play important roles in regulating proliferation and differentiation of plant-specific stem cells. Although receptors of CLEs are reported to be leucine-rich repeat receptor kinases, the mechanisms underlying CLE-induced receptor activation remain largely unknown. Here we show that SOMATIC EMBRYOGENESIS RECEPTOR KINASEs (SERKs) serve as co-receptors in CLE41/TDIF-PXY signaling to regulate plant vascular development. TDIF induces interaction of its receptor PXY with SERKs in vitro and in vivo. Furthermore, the serk1-1 serk2-1 bakl-5 mutant plants are less sensitive to TDIF, phenocopying the pxy mutant with a compromised promotion of procambial cell proliferation. Crystal structure of the PXY-TDIF-SERK2 complex reveals that the last amino acid of TDIF conserved among CLEs and other evolutionary-related peptides is important for the interaction between SERK2 and PXY. Taken together, our current study identifies SERKs as signaling components of the TDIF-PXY pathway and suggests a conserved activation mechanism of CLE receptors.展开更多
Cell division and differentiation of stem cells are controlled by non- cell-autonomous signals in higher organisms. The plant vascular meristem is a stem-cell tissue comprising procambial cells that produce xylem cell...Cell division and differentiation of stem cells are controlled by non- cell-autonomous signals in higher organisms. The plant vascular meristem is a stem-cell tissue comprising procambial cells that produce xylem cells on one side and phloem cells on the other side. Recent studies have revealed that TDIF (tracheary element differentiation inhibitory factor)/CLE41/CLE44 peptide signal controls the procambial cell fate in a non-cell-autonomous manner. TDIF produced in and secreted from phloem cells is perceived by TDR/PXY, a leucine-rich repeat receptor kinase located in the plasma membrane of procambial cells. This signal suppresses xylem cell differentiation of procambial cells and promotes their proliferation. In addition to TDIF, some other CLE peptides play roles in vascular development. Here, we summarize recent advances in CLE signaling governing vascular development.展开更多
Podoplanin (PDPN) is a mucin-type O-glycoprotein expressed in diverse cell types, such as lymphatic endothelial cells (LECs) in the vascular system and fibroblastic reticular cells (FRCs) in lymph nodes. PDPN on...Podoplanin (PDPN) is a mucin-type O-glycoprotein expressed in diverse cell types, such as lymphatic endothelial cells (LECs) in the vascular system and fibroblastic reticular cells (FRCs) in lymph nodes. PDPN on LECs or FRCs activates CLEC-2 in platelets, triggering platelet activation and/or aggregation through downstream signaling events, including activation of Syk kinase. This mechanism is required to initiate and maintain separation of blood and lymphatic vessels and to stabilize high endothelial venule integrity within lymph nodes. In the vascular system, normal expression of PDPN at the LEC surface requires transcriptional activation of Pdpn by Proxl and modification of PDPN with core 1-derived O-glycans. This review provides a comprehensive overview of the roles of PDPN in vascular development and lymphoid organ maintenance and discusses the mechanisms that regulate PDPN expression related to its function.展开更多
The plant vascular system consists of two conductive tissues, phloem and xylem. The vascular meristem, namely the (pro-)cambium, is a stem- cell tissue that gives rise to both xylem and phloem. Recent studies have r...The plant vascular system consists of two conductive tissues, phloem and xylem. The vascular meristem, namely the (pro-)cambium, is a stem- cell tissue that gives rise to both xylem and phloem. Recent studies have revealed that CLAVATA3/Embryo Surrounding Region-related (CLE) pep- tides function in establishing the vascular system through interaction with phytohormones. In particular, TDIF/CLE41/CLE44, phloem-derived CLE peptides, promote the proliferation of vascular cambium cells and prevent them from differentiating into xylem by regulating WOX4 expres- sion through the TDR/PXY receptor. In this review article, we outline recent advances on how CLE peptides function in vascular developmentin concert with phytohormones through mediating cell-cell communication. The perspective of CLE peptide signaling in vascular development is also discussed.展开更多
Ocular vessel networks develop in a highly stereotyped fashion.Abnormal ocular angiogenesis is associated with major diseases including age-related macular degeneration and diabetic retinopathy.Better understanding of...Ocular vessel networks develop in a highly stereotyped fashion.Abnormal ocular angiogenesis is associated with major diseases including age-related macular degeneration and diabetic retinopathy.Better understanding of mechanisms driving angiogenesis is expected to uncover novel targets to prevent vision loss.Capillary growth is driven by endothelial tip cells,which are selected by dynamic interplay between VEGF,Notch and BMP signaling,with VEGF acting as a positive regulator,and Notch and the BMP receptor Alk1 acting as negative regulators of tip cell formation.The concerted interplay between these molecules ensures that appropriate tip cell numbers leading new vessel branches are formed.In addition,guidance receptors including Neuropilins and Roundabout receptors contribute to vascular patterning by regulating VEGF and BMP signaling.Possibilities to target these pathways during pathological ocular neovascularization will be discussed.展开更多
Vascular tissues are very important for providing both mechanical strength and long-distance transport. The molecular mechanisms of regulation of vascular tissue develop- ment are still not fully understood. In this s...Vascular tissues are very important for providing both mechanical strength and long-distance transport. The molecular mechanisms of regulation of vascular tissue develop- ment are still not fully understood. In this study we identified ANACoo5 as a membrane-associated NAC family transcription factor that regulates vascular tissue development. Reporter gene assays showed that ANACoo5 was expressed mainly in the vascular tissues, increased expression of ANACoo5 protein in transgenic Arabidopsis caused dwarf phenotype, reduced xylem differentiation, decreased lignin content, repression of a lignin biosynthetic gene and genes related to cambium and primary wall, but activation of genes related to the secondary wall. Expression of a dominant repressor fusion of ANACoo5 had overall the opposite effects on vascular tissue differ- entiation and lignin synthetic gene expression. The ANACoo5- GFP fusion protein was localized at the plasma membrane, whereas deletion of the last 20 amino acids, which are mostly basic, caused its nuclear localization. These results indicate that ANACoo5 is a cell membrane-associated transcription factor that inhibits xylem tissue development in Arabidopsis.展开更多
Whether long non-coding RNA myocardial infarction-associated transcript is involved in oxygen-induced retinopathy remains poorly understood. To validate this hypothesis, we established a newborn mouse model of oxygen-...Whether long non-coding RNA myocardial infarction-associated transcript is involved in oxygen-induced retinopathy remains poorly understood. To validate this hypothesis, we established a newborn mouse model of oxygen-induced retinopathy by feeding in an oxygen concentration of 75 ± 2% from postnatal day 8 to postnatal day 12, followed by in normal air. On postnatal day 11, the mice were injected with the myocardial infarction-associated transcript siRNA plasmid via the vitreous cavity to knockdown long non-coding RNA myocardial infarction-associated transcript. Myocardial infarction-associated transcript siRNA transcription significantly inhibited myocardial infarctionassociated transcript mRNA expression, reduced the phosphatidylinosital-3-kinase, phosphorylated Akt and vascular endothelial growth factor immunopositivities, protein and mRNA expression, and alleviated the pathological damage to the retina of oxygen-induced retinopathy mouse models. These findings suggest that myocardial infarction-associated transcript is likely involved in the retinal neovascularization in retinopathy of prematurity and that inhibition of myocardial infarction-associated transcript can downregulate phosphatidylinosital-3-kinase, phosphorylated Akt and vascular endothelial growth factor expression levels and inhibit neovascularization. This study was approved by the Animal Ethics Committee of Shengjing Hospital of China Medical University, China(approval No. 2016 PS074 K) on February 25, 2016.展开更多
This study investigated the role of netrin-1 in placental vascular development. In vitro rat aortic ring assay and in vivo Matrigel plug assay were conducted to exmaine the effect of netrin-1 on angiogenesis. Human pl...This study investigated the role of netrin-1 in placental vascular development. In vitro rat aortic ring assay and in vivo Matrigel plug assay were conducted to exmaine the effect of netrin-1 on angiogenesis. Human placental microvascular endothelial cells (HPMECs) were isolated and cultured and their viability, migration and tubular formation were studied, in order to examine the effects of netrin-1. The results showed that netrin-1 potently stimulated neovascularization in a mouse Matrigel plug in vivo and the sprouting of endothelial cells in rat aortic rings in vitro. In addition, netrin-1 enhanced the viability, migration and tube formation of HPMECs. Our study suggested that netrin-1 could significantly promote the formation of blood vessels of human placenta and may be a potential target for developing new therapeutic strategies for placental vasculature-related diseases.展开更多
As an increasingly used alternative to perfluorooctanoic acid(PFOA),hexafluoropropylene oxide trimer acid(HFPO-TA)has been widely detected in global water environments.However,little is known regarding its toxic effec...As an increasingly used alternative to perfluorooctanoic acid(PFOA),hexafluoropropylene oxide trimer acid(HFPO-TA)has been widely detected in global water environments.However,little is known regarding its toxic effects on cardiovascular development.Here,zebrafish embryos were treated with egg water containing 0,60,120,or 240 mg/L HFPO-TA.Results showed that HFPO-TA treatment led to a significant reduction in both larval survival percentage and heart rate.Furthermore,HFPO-TA exposure caused severe pericardial edema and elongation of the sinus venous to bulbus arteriosus distance(SV-BA)in Tg(myl7:GFP)transgenic larvae,disrupting the expression of genes involved in heart development and thus causing abnormal heart looping.Obvious sprouting angiogenesis was observed in the 120 and 240 mg/L exposed Tg(fli:GFP)transgenic larvae.HFPO-TA treatment also impacted the mRNA levels of genes involved in the vascular endothelial growth factor(VEGF)pathway and embryonic vascular development.HFPO-TA exposure significantly decreased erythrocyte number in Tg(gata1:DsRed)transgenic embryos and influenced gene expression associated with the heme metabolism pathway.HFPO-TA also induced oxidative stress and altered the transcriptional levels of genes related to cell cycle and apoptosis,inhibiting cell proliferation while promoting apoptosis.Therefore,HFPO-TA exposure may induce abnormal development of the cardiovascular and hematopoietic systems in zebrafish embryos,suggesting it may not be a suitable or safe alternative for PFOA.展开更多
The emergence of the tracheophyte-based vascular system of land plants had major impacts on the evolution of terrestrial biology, in general, through its role in facilitating the development of plants with increased s...The emergence of the tracheophyte-based vascular system of land plants had major impacts on the evolution of terrestrial biology, in general, through its role in facilitating the development of plants with increased stature, photosynthetic output, and ability to colonize a greatly expanded range of environmental habitats. Recently, considerable progress has been made in terms of our understanding of the developmental and physiological programs involved in the formation and function of the plant vascular system. In this review, we first examine the evolutionary events that gave rise to the tracheophytes, followed by analysis of the genetic and hormonal networks that cooperate to orchestrate vascular development in the gymnosperms and angiosperms. The two essentialfunctions performed by the vascular system, namely the delivery of resources (water, essential mineral nutrients, sugars and amino acids) to the various plant organs and provision of mechanical support are next discussed. Here, we focus on critical questions relating to structural and physiological properties controlling the delivery of material through the xylem and phloem. Recent discoveries into the role of the vascular system as an effective long-distance communication system are next assessed in terms of the coordination of developmental, physiological and defense-related processes, at the whole-plant level. A concerted effort has been made to integrate all these new findings into a comprehensive picture of the state-of-the-art in the area of plant vascular biology. Finally, areas important for future research are highlighted in terms of their likely contribution both to basic knowledge and applications to primary industry.展开更多
Sevoflurane is the most commonly used volatile anesthetic during pregnancy.The viability of neural stem cells directly affects the development of the brain.However,it is unknown whether the use of sevoflurane during t...Sevoflurane is the most commonly used volatile anesthetic during pregnancy.The viability of neural stem cells directly affects the development of the brain.However,it is unknown whether the use of sevoflurane during the second trimester affects the survival of fetal neural stem cells.Therefore,in this study,we investigated whether exposure to sevoflurane in mid-gestation induces apoptosis of neural stem cells and behavioral abnormalities.On gestational day 14,pregnant rats were anesthetized with 2% or 3.5% sevoflurane for 2 hours.The offspring were weaned at 28 days and subjected to the Morris water maze test.The brains were harvested to examine neural stem cell apoptosis by immunofluorescence and to measure Nestin and SOX-2 levels by western blot assay at 6,24 and 48 hours after anesthesia as well as on postnatal day(P) 0,14 and 28.Vascular endothelial growth factor(VEGF) and phosphoinositide 3-kinase(PI3 K)/AKT pathway protein levels in fetal brain at 6 hours after anesthesia were assessed by western blot assay.Exposure to high-concentration(3.5%) sevoflurane during mid-gestation increased escape latency and path length to the platform,and it reduced the average duration spent in the target quadrant and platform crossing times.At 6,24 and 48 hours after anesthesia and at P0,P14 and P28,the percentage of Nestin/terminal deoxynucleotidyl transferase d UTP nick end labeling(TUNEL)-positive cells was increased,but Nestin and SOX-2 protein levels were decreased in the hippocampus of the offspring.At 6 hours after anesthesia,VEGF,PI3 K and phospho-AKT(p-AKT) levels were decreased in the fetal brain.These changes were not observed in animals given low-concentration(2%) sevoflurane exposure.Together,our findings indicate that exposure to a high concentration of sevoflurane(3.5%) in mid-gestation decreases VEGF,PI3 K and p-AKT protein levels and induces neural stem cell apoptosis,thereby causing learning and memory dysfunction in the offspring.展开更多
During plant development, the frequency and context of cell division must be controlled, and cells must differentiate properly to perform their mature functions. In addition, stem cell niches need to be maintained as ...During plant development, the frequency and context of cell division must be controlled, and cells must differentiate properly to perform their mature functions. In addition, stem cell niches need to be maintained as a reservoir for new cells. All of these processes require intercellular signaling, whether it is a cell relaying its position to other cells, or more mature cells signaling to the stem cell niche to regulate the rate of growth. Receptor-like kinases have emerged as a major component in these diverse roles, especially within the Arabidopsis root. In this review, the functions of receptor-like kinase signaling in regulating Arabidopsis root development will be examined in theareas of root apical meristem maintenance, regulation of epidermal cell fate, lateral root development and vascular differentiation.展开更多
基金supported by the National Natural Science Foundation of China,No.81801175(to CLT)the Fundamental Research Funds for the Central Universities of China,No.WK9110000044(to CLT)+2 种基金China Scholarship Council,No.201706270155(to CLT)the China Postdoctoral Science Foundation,No.2019M662179(to CLT)the Anhui Province Postdoctoral Science Foundation of China,No.2019B324(to CLT)
文摘Activin receptor-like kinase 1(ALK1)is a transmembrane serine/threonine receptor kinase of the transforming growth factor beta(TGFβ)receptor superfamily.ALK1 is specifically expressed in vascular endothelial cells,and its dynamic changes are closely related to the proliferation of endothelial cells,the recruitment of pericytes to blood vessels,and functional differentiation during embryonic vascular development.The pathophysiology of many cerebrovascular diseases is today understood as a disorder of endothelial cell function and an imbalance in the proportion of vascular cells.Indeed,mutations in ALK1 and its co-receptor endoglin are major genetic risk factors for vascular arteriovenous malformation.Many studies have shown that ALK1 is closely related to the development of cerebral aneurysms,arteriovenous malformations,and cerebral atherosclerosis.In this review,we describe the various roles of ALK1 in the regulation of angiogenesis and in the maintenance of cerebral vascular homeostasis,and we discuss its relationship to functional dysregulation in cerebrovascular diseases.This review should provide new perspectives for basic research on cerebrovascular diseases and offer more effective targets and strategies for clinical diagnosis,treatment,and prevention.
基金This work was supported by the National Natural Science Foundation of China(32071726 and 32271825).
文摘Secondary vascular development is a key biological characteristic of woody plants and the basis of wood formation.Our understanding of gene expression regulation and dynamic changes in microRNAs(miRNAs)during secondary vascular development is still limited.Here we present an integrated analysis of the miRNA and mRNA transcriptome of six phase-specific tissues-the shoot apex,procambium,primary vascular tissue,cambium,secondary phloem,and secondary xylem-in Populus tomentosa.Several novel regulatory modules,including the PtoTCP20-miR396d-PtoGRF15 module,were identified during secondary vascular development in Populus.A series of biochemical and molecular experiments confirmed that PtoTCP20 activated transcription of the miR396d precursor gene and that miR396d targeted PtoGRF15 to downregulate its expression.Plants overexpressing miR396d(35S:miR396d)showed enhanced secondary growth and increased xylem production.Conversely,during the transition from primary to secondary vascular development,plants with downregulated PtoTCP20expression(PtoTCP20-SRDX),downregulated miR396 expression(35S:STTM396),and PtoGRF15 overexpression(35S:PtoGRF15)showed delayed secondary growth.Novel regulatory modules were identified by integrated analysis of the miRNA and mRNA transcriptome,and the regulatory role of the PtoTCP20-miR396d-PtoGRF15 signaling cascade in secondary vascular development was validated in Populus,providing information to support improvements in forest cultivation and wood properties.
文摘Background: Hypertension, also known as increased blood pressure, is a phenomenon in which blood flows in blood vessels and causes persistently higher-than-normal pressure on the vessel wall. The identification of novel prognostic and pathogenesis biomarkers plays a key role in the management of hypertension. Methods: The GSE7483 and GSE75815 datasets from the gene expression omnibus (GEO) database were used to identify the genes associated with hypertension that were differentially expressed genes (DEGs). The functional role of the DEGs was elucidated by gene body (GO) enrichment analysis. In addition, we performed an immune infiltration assay and GSEA on the DEGs of hypertensive patients and verified the expression of novel DEGs in the blood of hypertensive patients by RT-qPCR. Results: A total of 267 DEGs were identified from the GEO database. GO analysis revealed that these genes were associated mainly with biological processes such as fibroblast proliferation, cell structural organization, extracellular matrix organization, vasculature development regulation, and angiogenesis. We identified five possible biomarkers, Ecm1, Sparc, Sphk1, Thbsl, and Mecp2, which correlate with vascular development and angiogenesis characteristic of hypertension by bioinformatics, and explored the clinical expression levels of these genes by RT-qPCR, and found that Sparc, Sphk1, and Thbs1 showed significant up-regulation, in agreement with the results of the bioinformatics analysis. Conclusion: Our study suggested that Sparc, Sphk1 and Thbs1 may be potential novel biomarkers for the diagnosis, treatment and prognosis of hypertension and that they are involved in the regulation of vascular development and angiogenesis in hypertension.
基金This research was funded by Projects of International Cooperation and Exchanges NSFC (31420103906), the National Science Foundation of China (31130063 and 31421001) and the Chinese Ministry of Science and Technology (2015CB910200) to J.C and the National Science Foun- dation of China (31370173) to L.Q.ACKNOWLEDGEMENTS We thank Jianhua He at Shanghai Synchrotron Radiation Facility (SSRF) for assistance with X-ray data collection, Dr. Hiroo Fukuda (Tokyo University, Japan) for the pxy-5 single mutant seeds, Dr. Libo Shah (Texas A&M University) for serk1-1 serk2-1^+/- bakl-5 mutant seeds, and Dr. Jia Li for other serk mutant seeds, SERK1, SERK2 entry vectors, and pSERKI: SERK1-GFP vector. No conflict of interest declared.
文摘In Arabidopsis, the CLAVATA3/EMBRYO SURROUNDING REGION-RELATED (CLE) peptides play important roles in regulating proliferation and differentiation of plant-specific stem cells. Although receptors of CLEs are reported to be leucine-rich repeat receptor kinases, the mechanisms underlying CLE-induced receptor activation remain largely unknown. Here we show that SOMATIC EMBRYOGENESIS RECEPTOR KINASEs (SERKs) serve as co-receptors in CLE41/TDIF-PXY signaling to regulate plant vascular development. TDIF induces interaction of its receptor PXY with SERKs in vitro and in vivo. Furthermore, the serk1-1 serk2-1 bakl-5 mutant plants are less sensitive to TDIF, phenocopying the pxy mutant with a compromised promotion of procambial cell proliferation. Crystal structure of the PXY-TDIF-SERK2 complex reveals that the last amino acid of TDIF conserved among CLEs and other evolutionary-related peptides is important for the interaction between SERK2 and PXY. Taken together, our current study identifies SERKs as signaling components of the TDIF-PXY pathway and suggests a conserved activation mechanism of CLE receptors.
基金supported in part by Grants-in-Aid from theMinistry of Education, Science, Sports and Culture of Japan(19060009) to HFsupported in part by Grants-in-Aid from the Japan Society for the Promotionof Science (20247003 to HF, JSPS Research Fellowships forYoung Scientists to YH)
文摘Cell division and differentiation of stem cells are controlled by non- cell-autonomous signals in higher organisms. The plant vascular meristem is a stem-cell tissue comprising procambial cells that produce xylem cells on one side and phloem cells on the other side. Recent studies have revealed that TDIF (tracheary element differentiation inhibitory factor)/CLE41/CLE44 peptide signal controls the procambial cell fate in a non-cell-autonomous manner. TDIF produced in and secreted from phloem cells is perceived by TDR/PXY, a leucine-rich repeat receptor kinase located in the plasma membrane of procambial cells. This signal suppresses xylem cell differentiation of procambial cells and promotes their proliferation. In addition to TDIF, some other CLE peptides play roles in vascular development. Here, we summarize recent advances in CLE signaling governing vascular development.
基金Acknowledgements This study was supported by a grant from the National Natural Science Foundation of China (No. 31400692).
文摘Podoplanin (PDPN) is a mucin-type O-glycoprotein expressed in diverse cell types, such as lymphatic endothelial cells (LECs) in the vascular system and fibroblastic reticular cells (FRCs) in lymph nodes. PDPN on LECs or FRCs activates CLEC-2 in platelets, triggering platelet activation and/or aggregation through downstream signaling events, including activation of Syk kinase. This mechanism is required to initiate and maintain separation of blood and lymphatic vessels and to stabilize high endothelial venule integrity within lymph nodes. In the vascular system, normal expression of PDPN at the LEC surface requires transcriptional activation of Pdpn by Proxl and modification of PDPN with core 1-derived O-glycans. This review provides a comprehensive overview of the roles of PDPN in vascular development and lymphoid organ maintenance and discusses the mechanisms that regulate PDPN expression related to its function.
基金supported by the National Natural Science Foundation ofChina (31271575 31200902)+1 种基金the Fundamental ResearchFunds for the Central Universities (GK201103005)the Specialized Research Fund for the Doctoral Program of Higher Education from the Ministry of Education of China(20120202120009)
文摘The plant vascular system consists of two conductive tissues, phloem and xylem. The vascular meristem, namely the (pro-)cambium, is a stem- cell tissue that gives rise to both xylem and phloem. Recent studies have revealed that CLAVATA3/Embryo Surrounding Region-related (CLE) pep- tides function in establishing the vascular system through interaction with phytohormones. In particular, TDIF/CLE41/CLE44, phloem-derived CLE peptides, promote the proliferation of vascular cambium cells and prevent them from differentiating into xylem by regulating WOX4 expres- sion through the TDR/PXY receptor. In this review article, we outline recent advances on how CLE peptides function in vascular developmentin concert with phytohormones through mediating cell-cell communication. The perspective of CLE peptide signaling in vascular development is also discussed.
文摘Ocular vessel networks develop in a highly stereotyped fashion.Abnormal ocular angiogenesis is associated with major diseases including age-related macular degeneration and diabetic retinopathy.Better understanding of mechanisms driving angiogenesis is expected to uncover novel targets to prevent vision loss.Capillary growth is driven by endothelial tip cells,which are selected by dynamic interplay between VEGF,Notch and BMP signaling,with VEGF acting as a positive regulator,and Notch and the BMP receptor Alk1 acting as negative regulators of tip cell formation.The concerted interplay between these molecules ensures that appropriate tip cell numbers leading new vessel branches are formed.In addition,guidance receptors including Neuropilins and Roundabout receptors contribute to vascular patterning by regulating VEGF and BMP signaling.Possibilities to target these pathways during pathological ocular neovascularization will be discussed.
基金supported by the National High Technology Research and Development Program of China(2012AA101108)National Natural Science Foundation of China(31171614)Ministry of Agriculture of China(2014ZX08001)
文摘Vascular tissues are very important for providing both mechanical strength and long-distance transport. The molecular mechanisms of regulation of vascular tissue develop- ment are still not fully understood. In this study we identified ANACoo5 as a membrane-associated NAC family transcription factor that regulates vascular tissue development. Reporter gene assays showed that ANACoo5 was expressed mainly in the vascular tissues, increased expression of ANACoo5 protein in transgenic Arabidopsis caused dwarf phenotype, reduced xylem differentiation, decreased lignin content, repression of a lignin biosynthetic gene and genes related to cambium and primary wall, but activation of genes related to the secondary wall. Expression of a dominant repressor fusion of ANACoo5 had overall the opposite effects on vascular tissue differ- entiation and lignin synthetic gene expression. The ANACoo5- GFP fusion protein was localized at the plasma membrane, whereas deletion of the last 20 amino acids, which are mostly basic, caused its nuclear localization. These results indicate that ANACoo5 is a cell membrane-associated transcription factor that inhibits xylem tissue development in Arabidopsis.
基金supported by the National Natural Science Foundation of China,No.81600747(to YD)the Start-Up Foundation for Doctors of Liaoning Province,China,No.201501020(to YD)。
文摘Whether long non-coding RNA myocardial infarction-associated transcript is involved in oxygen-induced retinopathy remains poorly understood. To validate this hypothesis, we established a newborn mouse model of oxygen-induced retinopathy by feeding in an oxygen concentration of 75 ± 2% from postnatal day 8 to postnatal day 12, followed by in normal air. On postnatal day 11, the mice were injected with the myocardial infarction-associated transcript siRNA plasmid via the vitreous cavity to knockdown long non-coding RNA myocardial infarction-associated transcript. Myocardial infarction-associated transcript siRNA transcription significantly inhibited myocardial infarctionassociated transcript mRNA expression, reduced the phosphatidylinosital-3-kinase, phosphorylated Akt and vascular endothelial growth factor immunopositivities, protein and mRNA expression, and alleviated the pathological damage to the retina of oxygen-induced retinopathy mouse models. These findings suggest that myocardial infarction-associated transcript is likely involved in the retinal neovascularization in retinopathy of prematurity and that inhibition of myocardial infarction-associated transcript can downregulate phosphatidylinosital-3-kinase, phosphorylated Akt and vascular endothelial growth factor expression levels and inhibit neovascularization. This study was approved by the Animal Ethics Committee of Shengjing Hospital of China Medical University, China(approval No. 2016 PS074 K) on February 25, 2016.
基金supported by a grant from the National Nature Sciences Foundation of China (No. 30872776)
文摘This study investigated the role of netrin-1 in placental vascular development. In vitro rat aortic ring assay and in vivo Matrigel plug assay were conducted to exmaine the effect of netrin-1 on angiogenesis. Human placental microvascular endothelial cells (HPMECs) were isolated and cultured and their viability, migration and tubular formation were studied, in order to examine the effects of netrin-1. The results showed that netrin-1 potently stimulated neovascularization in a mouse Matrigel plug in vivo and the sprouting of endothelial cells in rat aortic rings in vitro. In addition, netrin-1 enhanced the viability, migration and tube formation of HPMECs. Our study suggested that netrin-1 could significantly promote the formation of blood vessels of human placenta and may be a potential target for developing new therapeutic strategies for placental vasculature-related diseases.
基金supported by the Ministry of Science and Technology of China(Nos.2021YFA1101300 and 2020YFA0112500)the National Key R&D Program of China(2018YFA0801000)the National Natural Science Foundation of China(No.32170853)。
文摘As an increasingly used alternative to perfluorooctanoic acid(PFOA),hexafluoropropylene oxide trimer acid(HFPO-TA)has been widely detected in global water environments.However,little is known regarding its toxic effects on cardiovascular development.Here,zebrafish embryos were treated with egg water containing 0,60,120,or 240 mg/L HFPO-TA.Results showed that HFPO-TA treatment led to a significant reduction in both larval survival percentage and heart rate.Furthermore,HFPO-TA exposure caused severe pericardial edema and elongation of the sinus venous to bulbus arteriosus distance(SV-BA)in Tg(myl7:GFP)transgenic larvae,disrupting the expression of genes involved in heart development and thus causing abnormal heart looping.Obvious sprouting angiogenesis was observed in the 120 and 240 mg/L exposed Tg(fli:GFP)transgenic larvae.HFPO-TA treatment also impacted the mRNA levels of genes involved in the vascular endothelial growth factor(VEGF)pathway and embryonic vascular development.HFPO-TA exposure significantly decreased erythrocyte number in Tg(gata1:DsRed)transgenic embryos and influenced gene expression associated with the heme metabolism pathway.HFPO-TA also induced oxidative stress and altered the transcriptional levels of genes related to cell cycle and apoptosis,inhibiting cell proliferation while promoting apoptosis.Therefore,HFPO-TA exposure may induce abnormal development of the cardiovascular and hematopoietic systems in zebrafish embryos,suggesting it may not be a suitable or safe alternative for PFOA.
基金supported in part by the National Science Foundation (grants IOS-0752997 and IOS-0918433 to WJL grants IOS#0749731, IOS#051909 to PK)+8 种基金the Department of Energy, Division of Energy Biosciences (grantsDE-FG02-94ER20134 to WJL)the US Department of Agriculture, Agricultural Research Service (under Agreement number58-6250-0-008 to MAG)the Spanish Ministry of Science andInnovation (MICINN) (grants AGL2007-61948 and AGL2009-09018 to AFLM)the Ministry of Education, Science, Sportsand Culture of Japan (grant 19060009 to HF)the JapanSociety for the Promotion of Science (JSPS grant 23227001to HF)the NC-CARP project (to HF)the NationalKey Basic Research Program of China (grant 2012CB114500to XH)the National Natural Science Foundation of China (grant31070156 to XH)the NSFC-JSPS cooperation project(grant 31011140070 to HF and XH)
文摘The emergence of the tracheophyte-based vascular system of land plants had major impacts on the evolution of terrestrial biology, in general, through its role in facilitating the development of plants with increased stature, photosynthetic output, and ability to colonize a greatly expanded range of environmental habitats. Recently, considerable progress has been made in terms of our understanding of the developmental and physiological programs involved in the formation and function of the plant vascular system. In this review, we first examine the evolutionary events that gave rise to the tracheophytes, followed by analysis of the genetic and hormonal networks that cooperate to orchestrate vascular development in the gymnosperms and angiosperms. The two essentialfunctions performed by the vascular system, namely the delivery of resources (water, essential mineral nutrients, sugars and amino acids) to the various plant organs and provision of mechanical support are next discussed. Here, we focus on critical questions relating to structural and physiological properties controlling the delivery of material through the xylem and phloem. Recent discoveries into the role of the vascular system as an effective long-distance communication system are next assessed in terms of the coordination of developmental, physiological and defense-related processes, at the whole-plant level. A concerted effort has been made to integrate all these new findings into a comprehensive picture of the state-of-the-art in the area of plant vascular biology. Finally, areas important for future research are highlighted in terms of their likely contribution both to basic knowledge and applications to primary industry.
基金supported by the National Natural Science Foundation of China,No.81671311(to PZ),No.81503273(to NZ)the Science and Technology Foundation of Liaoning Province of China,No.2015020467(to PZ)the Outstanding Scientific Fund of Shengjing Hospital of China Medical University,No.201708
文摘Sevoflurane is the most commonly used volatile anesthetic during pregnancy.The viability of neural stem cells directly affects the development of the brain.However,it is unknown whether the use of sevoflurane during the second trimester affects the survival of fetal neural stem cells.Therefore,in this study,we investigated whether exposure to sevoflurane in mid-gestation induces apoptosis of neural stem cells and behavioral abnormalities.On gestational day 14,pregnant rats were anesthetized with 2% or 3.5% sevoflurane for 2 hours.The offspring were weaned at 28 days and subjected to the Morris water maze test.The brains were harvested to examine neural stem cell apoptosis by immunofluorescence and to measure Nestin and SOX-2 levels by western blot assay at 6,24 and 48 hours after anesthesia as well as on postnatal day(P) 0,14 and 28.Vascular endothelial growth factor(VEGF) and phosphoinositide 3-kinase(PI3 K)/AKT pathway protein levels in fetal brain at 6 hours after anesthesia were assessed by western blot assay.Exposure to high-concentration(3.5%) sevoflurane during mid-gestation increased escape latency and path length to the platform,and it reduced the average duration spent in the target quadrant and platform crossing times.At 6,24 and 48 hours after anesthesia and at P0,P14 and P28,the percentage of Nestin/terminal deoxynucleotidyl transferase d UTP nick end labeling(TUNEL)-positive cells was increased,but Nestin and SOX-2 protein levels were decreased in the hippocampus of the offspring.At 6 hours after anesthesia,VEGF,PI3 K and phospho-AKT(p-AKT) levels were decreased in the fetal brain.These changes were not observed in animals given low-concentration(2%) sevoflurane exposure.Together,our findings indicate that exposure to a high concentration of sevoflurane(3.5%) in mid-gestation decreases VEGF,PI3 K and p-AKT protein levels and induces neural stem cell apoptosis,thereby causing learning and memory dysfunction in the offspring.
文摘During plant development, the frequency and context of cell division must be controlled, and cells must differentiate properly to perform their mature functions. In addition, stem cell niches need to be maintained as a reservoir for new cells. All of these processes require intercellular signaling, whether it is a cell relaying its position to other cells, or more mature cells signaling to the stem cell niche to regulate the rate of growth. Receptor-like kinases have emerged as a major component in these diverse roles, especially within the Arabidopsis root. In this review, the functions of receptor-like kinase signaling in regulating Arabidopsis root development will be examined in theareas of root apical meristem maintenance, regulation of epidermal cell fate, lateral root development and vascular differentiation.