Early growth response protein 1(Egr-1)triggers the transcription of many genes involved in cell growth,differentiation,synaptic plasticity,and neurogenesis.However,its mechanism in neuronal survival and degeneration i...Early growth response protein 1(Egr-1)triggers the transcription of many genes involved in cell growth,differentiation,synaptic plasticity,and neurogenesis.However,its mechanism in neuronal survival and degeneration is still poorly understood.This study demonstrated that Egr-1 was down-regulated at mRNA and protein levels in the central nervous system(CNS)of experimental autoimmune encephalomyelitis(EAE)mice.Egr-1 knockout exacerbated EAE progression in mice,as shown by increased disease severity and incidence;it also aggravated neuronal apoptosis,which was associated with weakened activation of the BDNF/TGFβ1/MAPK/Akt signaling pathways in the CNS of EAE mice.Consistently,Egr-1 siRNA promoted apoptosis but mitigated the activation of BDNF/TGFβ1/MAPK/Akt signaling in SH-SY5Y cells.Our results revealed that Egr-1 is a crucial regulator of neuronal survival in EAE by regulating TGFβ1-mediated signaling activation,implicating the important role of Egr-1 in the pathogenesis of multiple sclerosis as a potential novel therapy target.展开更多
Insufficient remyelination due to impaired oligodendrocyte precursor cell(OPC)differentiation and maturation is strongly associated with irreversible white matter injury(WMI)and neurological deficits.We analyzed whole...Insufficient remyelination due to impaired oligodendrocyte precursor cell(OPC)differentiation and maturation is strongly associated with irreversible white matter injury(WMI)and neurological deficits.We analyzed whole transcriptome expression to elucidate the potential role and underlying mechanism of action of lipocalin-2(LCN2)in OPC differentiation and WMI and identified the receptor SCL22A17 and downstream transcription factor early growth response protein 1(EGR1)as the key signals contributing to LCN2-mediated insufficient OPC remyelination.In LCN-knockdown and OPC EGR1 conditional-knockout mice,we discovered enhanced OPC differentiation in developing and injured white matter(WM);consistent with this,the specific inactivation of LCN2/SCl22A17/EGR1 signaling promoted remyelination and neurological recovery in both atypical,acute WMI due to subarachnoid hemorrhage and typical,chronic WMI due to multiple sclerosis.This potentially represents a novel strategy to enhance differentiation and remyelination in patients with white matter injury.展开更多
The molecular cascade underlying tendon formation starts when progenitor cells begin to express the Scleraxis(Scx)gene.Scx knockout mice develop some but not all tendons,suggesting that additional factors are necessar...The molecular cascade underlying tendon formation starts when progenitor cells begin to express the Scleraxis(Scx)gene.Scx knockout mice develop some but not all tendons,suggesting that additional factors are necessary for tendon commitment,maintenance,and differentiation.Other transcription factors,such as Mohawk(Mkx)or early growth response(Egr),maintain Scx expression and extracellular matrix formation during fibrillogenesis.The inhibition of wingless and int-related protein signaling is necessary and sufficient to induce the expression of Scx.Once the commitment of tenogenic lineage occurs,transforming growth factor-beta(TGFβ)induces the Scx gene expression,becoming involved in the maintenance of tendon cell fate.From this point of view,we discussed two phases of the tenogenic process during limb development:dependent and independent of mechanical forces.Finally,we highlight the importance of understanding embryonic tendon development to improve therapeutic strategies in regenerative medicines for tendons.展开更多
The phytohormones are pivotal chemical messengers produced within the plant that regulate its growth and development, and responses to environmental stimuli. Drought and salinity are adverse environmental factors that...The phytohormones are pivotal chemical messengers produced within the plant that regulate its growth and development, and responses to environmental stimuli. Drought and salinity are adverse environmental factors that disturb the plant hormonal balance. Accordingly, these hormonal fluctuations modify the cellular dynamic and hence they play a central role in regulating plant growth responses to abiotic stresses such as drought and salinity. The present review gives an update about the alterations of endogenous phytohormones such as abscisic acid (ABA), auxins (Aux), cytokinins (CKs), ethylene (ET), gibberellins (GAs), jasmonates (JAs), salicylic acid (SA), brassinosteroids (BRs), strigolactones (SLs) and nitric oxide (NO) that occur as part of the adaptative responses of plant against drought and salt stresses. Better understanding of the endogenous hormonal changes during the plant response to both abiotic stresses will contribute, in part, to the development of stress-tolerant plants.展开更多
Schizophrenia(SCZ)is the most common serious mental illness with a high disability rate and heavy social and family burdens.At present,there is no clear etiology and pathogenesis of schizophrenia.Studies have shown th...Schizophrenia(SCZ)is the most common serious mental illness with a high disability rate and heavy social and family burdens.At present,there is no clear etiology and pathogenesis of schizophrenia.Studies have shown that the occurrence of schizophrenia may be related to the abnormality of the hypothalamic-pituitary-adrenal(HPA)axis.The LIM-homeobox gene 3(LHXS)and early growth response 1(EGR1)can affect pituitary function.Because the synapsin 2(SYN2)gene polymorphism regulates the activity of LHX3 and EGR1,it may cause the occurrence of schizophrenia.This article will review the possible involvement of SYN2 gene polymorphism in the pathogenesis of schizophrenia via regulating the activity of LHX3 and EGR1,then to afiect the HPA axis.展开更多
The changes in external K^+ concentration affect plant root growth. However, the molecular mechanism for perceiving a K^+ signal to modulate root growth remains unknown. It is hypothesized that the K^+ channel AKT1 is...The changes in external K^+ concentration affect plant root growth. However, the molecular mechanism for perceiving a K^+ signal to modulate root growth remains unknown. It is hypothesized that the K^+ channel AKT1 is involved in low K^+ sensing in the Arabidopsis root and subsequent regulation of root growth. Along with the decline of external K^+ concentration, the primary root growth of wild-type plants was gradually inhibited.However, the primary root of the akt1 mutant could still grow under low K^+ (LK) conditions. Application of NAA inhibited akt1 root growth, but promoted wild-type root growth under LK conditions. By using the Pro DR5:GFP and Pro PIN1:PIN1-GFP lines, we found that LK treatment reduced auxin accumulation in wild-type root tips by degrading PIN1 proteins, which did not occur in the akt1 mutant. The LK-induced PIN1 degradation may be due to the inhibition of vesicle trafficking of PIN1 proteins. In conclusion, our findings indicate that AKT1 is required for an Arabidopsis response to changes in external K^+ , and subsequent regulation of K^+ -dependent root growth by modulating PIN1 degradation and auxin redistribution in the root.展开更多
基金supported by the National Natural Science Foundation of China(82074043,82104425,82374065,and 81673626)the China Postdoctoral Science Foundation(2021M702217).
文摘Early growth response protein 1(Egr-1)triggers the transcription of many genes involved in cell growth,differentiation,synaptic plasticity,and neurogenesis.However,its mechanism in neuronal survival and degeneration is still poorly understood.This study demonstrated that Egr-1 was down-regulated at mRNA and protein levels in the central nervous system(CNS)of experimental autoimmune encephalomyelitis(EAE)mice.Egr-1 knockout exacerbated EAE progression in mice,as shown by increased disease severity and incidence;it also aggravated neuronal apoptosis,which was associated with weakened activation of the BDNF/TGFβ1/MAPK/Akt signaling pathways in the CNS of EAE mice.Consistently,Egr-1 siRNA promoted apoptosis but mitigated the activation of BDNF/TGFβ1/MAPK/Akt signaling in SH-SY5Y cells.Our results revealed that Egr-1 is a crucial regulator of neuronal survival in EAE by regulating TGFβ1-mediated signaling activation,implicating the important role of Egr-1 in the pathogenesis of multiple sclerosis as a potential novel therapy target.
基金This work was supported by the National Natural Science Foundation of China(81901216 and 82030036)Southwest Hospital(SWH2018BJKJ-05 and SWH2015QN13)the Chongqing Talent Program(4139Z2391).
文摘Insufficient remyelination due to impaired oligodendrocyte precursor cell(OPC)differentiation and maturation is strongly associated with irreversible white matter injury(WMI)and neurological deficits.We analyzed whole transcriptome expression to elucidate the potential role and underlying mechanism of action of lipocalin-2(LCN2)in OPC differentiation and WMI and identified the receptor SCL22A17 and downstream transcription factor early growth response protein 1(EGR1)as the key signals contributing to LCN2-mediated insufficient OPC remyelination.In LCN-knockdown and OPC EGR1 conditional-knockout mice,we discovered enhanced OPC differentiation in developing and injured white matter(WM);consistent with this,the specific inactivation of LCN2/SCl22A17/EGR1 signaling promoted remyelination and neurological recovery in both atypical,acute WMI due to subarachnoid hemorrhage and typical,chronic WMI due to multiple sclerosis.This potentially represents a novel strategy to enhance differentiation and remyelination in patients with white matter injury.
基金supported by the Dirección General de Asuntos del Personal Académico(DGAPA)-Universidad Nacional Autónoma de México[Grant No.IN213314]Consejo Nacional de Ciencia y Tecnología(CONACyT)[Grant No.1887 CONACyTFronteras de la Ciencia]awarded to JC-M.
文摘The molecular cascade underlying tendon formation starts when progenitor cells begin to express the Scleraxis(Scx)gene.Scx knockout mice develop some but not all tendons,suggesting that additional factors are necessary for tendon commitment,maintenance,and differentiation.Other transcription factors,such as Mohawk(Mkx)or early growth response(Egr),maintain Scx expression and extracellular matrix formation during fibrillogenesis.The inhibition of wingless and int-related protein signaling is necessary and sufficient to induce the expression of Scx.Once the commitment of tenogenic lineage occurs,transforming growth factor-beta(TGFβ)induces the Scx gene expression,becoming involved in the maintenance of tendon cell fate.From this point of view,we discussed two phases of the tenogenic process during limb development:dependent and independent of mechanical forces.Finally,we highlight the importance of understanding embryonic tendon development to improve therapeutic strategies in regenerative medicines for tendons.
文摘The phytohormones are pivotal chemical messengers produced within the plant that regulate its growth and development, and responses to environmental stimuli. Drought and salinity are adverse environmental factors that disturb the plant hormonal balance. Accordingly, these hormonal fluctuations modify the cellular dynamic and hence they play a central role in regulating plant growth responses to abiotic stresses such as drought and salinity. The present review gives an update about the alterations of endogenous phytohormones such as abscisic acid (ABA), auxins (Aux), cytokinins (CKs), ethylene (ET), gibberellins (GAs), jasmonates (JAs), salicylic acid (SA), brassinosteroids (BRs), strigolactones (SLs) and nitric oxide (NO) that occur as part of the adaptative responses of plant against drought and salt stresses. Better understanding of the endogenous hormonal changes during the plant response to both abiotic stresses will contribute, in part, to the development of stress-tolerant plants.
基金Yunnan Provincial Department of Science and Technology Project(202101AY070001-224).
文摘Schizophrenia(SCZ)is the most common serious mental illness with a high disability rate and heavy social and family burdens.At present,there is no clear etiology and pathogenesis of schizophrenia.Studies have shown that the occurrence of schizophrenia may be related to the abnormality of the hypothalamic-pituitary-adrenal(HPA)axis.The LIM-homeobox gene 3(LHXS)and early growth response 1(EGR1)can affect pituitary function.Because the synapsin 2(SYN2)gene polymorphism regulates the activity of LHX3 and EGR1,it may cause the occurrence of schizophrenia.This article will review the possible involvement of SYN2 gene polymorphism in the pathogenesis of schizophrenia via regulating the activity of LHX3 and EGR1,then to afiect the HPA axis.
基金supported by grants from the National Natural Science Foundation of China(31570243No.31622008No.31421062)
文摘The changes in external K^+ concentration affect plant root growth. However, the molecular mechanism for perceiving a K^+ signal to modulate root growth remains unknown. It is hypothesized that the K^+ channel AKT1 is involved in low K^+ sensing in the Arabidopsis root and subsequent regulation of root growth. Along with the decline of external K^+ concentration, the primary root growth of wild-type plants was gradually inhibited.However, the primary root of the akt1 mutant could still grow under low K^+ (LK) conditions. Application of NAA inhibited akt1 root growth, but promoted wild-type root growth under LK conditions. By using the Pro DR5:GFP and Pro PIN1:PIN1-GFP lines, we found that LK treatment reduced auxin accumulation in wild-type root tips by degrading PIN1 proteins, which did not occur in the akt1 mutant. The LK-induced PIN1 degradation may be due to the inhibition of vesicle trafficking of PIN1 proteins. In conclusion, our findings indicate that AKT1 is required for an Arabidopsis response to changes in external K^+ , and subsequent regulation of K^+ -dependent root growth by modulating PIN1 degradation and auxin redistribution in the root.