Monocyte-to-M0/M1 macrophage differentiation with unclear molecular mechanisms is a pivotal cellular event in many cardiovascular diseases including atherosclerosis.Long non-coding RNAs(lncRNAs)are a group of protein ...Monocyte-to-M0/M1 macrophage differentiation with unclear molecular mechanisms is a pivotal cellular event in many cardiovascular diseases including atherosclerosis.Long non-coding RNAs(lncRNAs)are a group of protein expression regulators;however,the roles of monocyte-lncRNAs in macrophage differentiation and its related vascular diseases are still unclear.The study aims to investigate whether the novel leukocyte-specific lncRNA Morrbid could regulate macrophage differentiation and atherogenesis.We identified that Morrbid was increased in monocytes and arterial walls from atherosclerotic mouse and from patients with atherosclerosis.In cultured monocytes,Morrbid expression was markedly increased during monocyte to M0 macrophage differentiation with an additional increase during M0 macrophage-to-M1 macrophage differentiation.The differentiation stimuli-induced monocyte-macrophage differentiation and the macrophage activity were inhibited by Morrbid knockdown.Moreover,overexpression of Morrbid alone was sufficient to elicit the monocyte-macrophage differentiation.The role of Morrbid in monocyte-macrophage differentiation was also identified in vivo in atherosclerotic mice and was verified in Morrbid knockout mice.We identified that PI3-kinase/Akt was involved in the up-regulation of Morrbid expression,whereas s100a10 was involved in Morrbid-mediated effect on macrophage differentiation.To provide a proof of concept of Morrbid in pathogenesis of monocyte/macrophage-related vascular disease,we applied an acute atherosclerosis model in mice.The results revealed that overexpression of Morrbid enhanced but monocyte/macrophage-specific Morrbid knockout inhibited the monocytes/macrophages recruitment and atherosclerotic lesion formation in mice.The results suggest that Morrbid is a novel biomarker and a modulator of monocyte-macrophage phenotypes,which is involved in atherogenesis.展开更多
Background Ischaemic stroke and other cardiovascular illnesses are characterised by abnormalities in the processes of thrombosis and haemostasis,which rely on platelet activity.In platelets,a wide variety of microRNAs...Background Ischaemic stroke and other cardiovascular illnesses are characterised by abnormalities in the processes of thrombosis and haemostasis,which rely on platelet activity.In platelets,a wide variety of microRNAs(long non-coding RNA,lncRNAs)is found.Due to the absence of nuclear DNA in platelets,lncRNAs may serve as critical post-transcriptional regulators of platelet activities.However,research into the roles of lncRNAs in platelets is limited.Objective The purpose of this study is to learn more about the molecular mechanism by which MALAT1 affects platelet activity and thrombus formation.Methods/results The CD34+megakaryocytes used in this research as an in vitro model for human megakaryocytes and platelets.Cell adhesion and spreading are enhanced in the absence and presence of agonists in CD34+megakaryocytes subjected to MALAT1 knockdown(KD).The adhesion and activity of platelet-like particles produced by MALAT1 KD cells are significantly enhanced at rest and after thrombin activation.Thrombus development on a collagen matrix is also greatly enhanced in the microfluidic whole-blood perfusion model:platelets lacking MALAT1 exhibit elevated accumulation,distributing area and activity.In addition,MALAT1-deficient mice bleed less and form a stable occlusive thrombus more quickly than wild-type mice.PTEN and PDK1 regulated the activity of MALAT1 in platelets to carry out its PI3k/Akt/GSK-3βsignalling pathway-related function.Conclusion The suppression of MALAT1 expression significantly increases platelet adhesion,spreading,platelet activity,and thrombus formation.lncRNAs may constitute a unique class of platelet function modulators.展开更多
Half-smooth tongue sole (Cynoglossus semilaevis) is a rare marine flatfish whose mature ovary and testis greatly differ in volume and weight. The length and weight of mature females are over twice greater than those...Half-smooth tongue sole (Cynoglossus semilaevis) is a rare marine flatfish whose mature ovary and testis greatly differ in volume and weight. The length and weight of mature females are over twice greater than those of mature males. To obtain sufficient information on gonad differentiation and the relationship between gonad development and growth in the fish, we compared gene expression between the ovary and testis using suppression subtractive hybridization (SSH). Testis cDNAs are subtracted from ovary cDNAs and are used to es- tablish an ovary testis-subtracted cDNA library. A total of 41 nonredundant clones are identified, including 20 known cDNAs, 9 unchar-acterized cDNAs (EST clones), and 12 novel sequences. For selected genes such as ZPC, RacGAP, survivin, aquaporin, CPEB, O5, O15, and O18, gene expression patterns are analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). The results confirm that these genes are only expressed in the ovary and not in the testis, or at higher levels in the ovary than in the testis. At the same time, expressions of certain genes such as ZPC, survivin, aquaporin, CPEB, and O15 are demonstrated to possess sexual dimorphism in the kidney or muscle, and spleen. The results suggest that these genes could play key roles not only in the ovary but in other female tissues as well.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.82030007,81670398,and 91639102)the Central Government Guides Local Science and Technology Development Project(Grant No.2022ZYD0057)+2 种基金the Sichuan Science and Technology Program(Grant Nos.2022YFS0578 and 2022YFS0614)the Start-up Research Fund of Southwest Medical University(Grant No.00040155)supported in part by the Start-up fund from the University of Alabama at Birmingham.
文摘Monocyte-to-M0/M1 macrophage differentiation with unclear molecular mechanisms is a pivotal cellular event in many cardiovascular diseases including atherosclerosis.Long non-coding RNAs(lncRNAs)are a group of protein expression regulators;however,the roles of monocyte-lncRNAs in macrophage differentiation and its related vascular diseases are still unclear.The study aims to investigate whether the novel leukocyte-specific lncRNA Morrbid could regulate macrophage differentiation and atherogenesis.We identified that Morrbid was increased in monocytes and arterial walls from atherosclerotic mouse and from patients with atherosclerosis.In cultured monocytes,Morrbid expression was markedly increased during monocyte to M0 macrophage differentiation with an additional increase during M0 macrophage-to-M1 macrophage differentiation.The differentiation stimuli-induced monocyte-macrophage differentiation and the macrophage activity were inhibited by Morrbid knockdown.Moreover,overexpression of Morrbid alone was sufficient to elicit the monocyte-macrophage differentiation.The role of Morrbid in monocyte-macrophage differentiation was also identified in vivo in atherosclerotic mice and was verified in Morrbid knockout mice.We identified that PI3-kinase/Akt was involved in the up-regulation of Morrbid expression,whereas s100a10 was involved in Morrbid-mediated effect on macrophage differentiation.To provide a proof of concept of Morrbid in pathogenesis of monocyte/macrophage-related vascular disease,we applied an acute atherosclerosis model in mice.The results revealed that overexpression of Morrbid enhanced but monocyte/macrophage-specific Morrbid knockout inhibited the monocytes/macrophages recruitment and atherosclerotic lesion formation in mice.The results suggest that Morrbid is a novel biomarker and a modulator of monocyte-macrophage phenotypes,which is involved in atherogenesis.
基金This work was supported by Provincial Natural Science Foundation of Shandong Province(Grant No.ZR2021MH082)This work was also supported by the National Natural Science Foundation of China(Grant No.81801192 and 91639102)the funding of Taishan Scholars of Shan-dong Province to Binzhou Medical University.
文摘Background Ischaemic stroke and other cardiovascular illnesses are characterised by abnormalities in the processes of thrombosis and haemostasis,which rely on platelet activity.In platelets,a wide variety of microRNAs(long non-coding RNA,lncRNAs)is found.Due to the absence of nuclear DNA in platelets,lncRNAs may serve as critical post-transcriptional regulators of platelet activities.However,research into the roles of lncRNAs in platelets is limited.Objective The purpose of this study is to learn more about the molecular mechanism by which MALAT1 affects platelet activity and thrombus formation.Methods/results The CD34+megakaryocytes used in this research as an in vitro model for human megakaryocytes and platelets.Cell adhesion and spreading are enhanced in the absence and presence of agonists in CD34+megakaryocytes subjected to MALAT1 knockdown(KD).The adhesion and activity of platelet-like particles produced by MALAT1 KD cells are significantly enhanced at rest and after thrombin activation.Thrombus development on a collagen matrix is also greatly enhanced in the microfluidic whole-blood perfusion model:platelets lacking MALAT1 exhibit elevated accumulation,distributing area and activity.In addition,MALAT1-deficient mice bleed less and form a stable occlusive thrombus more quickly than wild-type mice.PTEN and PDK1 regulated the activity of MALAT1 in platelets to carry out its PI3k/Akt/GSK-3βsignalling pathway-related function.Conclusion The suppression of MALAT1 expression significantly increases platelet adhesion,spreading,platelet activity,and thrombus formation.lncRNAs may constitute a unique class of platelet function modulators.
基金supported by the National High Tech-nology Research and Development Program of China (No. 2006AA10A404)the National Natural Science Foundation of China (No. 30671624)
文摘Half-smooth tongue sole (Cynoglossus semilaevis) is a rare marine flatfish whose mature ovary and testis greatly differ in volume and weight. The length and weight of mature females are over twice greater than those of mature males. To obtain sufficient information on gonad differentiation and the relationship between gonad development and growth in the fish, we compared gene expression between the ovary and testis using suppression subtractive hybridization (SSH). Testis cDNAs are subtracted from ovary cDNAs and are used to es- tablish an ovary testis-subtracted cDNA library. A total of 41 nonredundant clones are identified, including 20 known cDNAs, 9 unchar-acterized cDNAs (EST clones), and 12 novel sequences. For selected genes such as ZPC, RacGAP, survivin, aquaporin, CPEB, O5, O15, and O18, gene expression patterns are analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). The results confirm that these genes are only expressed in the ovary and not in the testis, or at higher levels in the ovary than in the testis. At the same time, expressions of certain genes such as ZPC, survivin, aquaporin, CPEB, and O15 are demonstrated to possess sexual dimorphism in the kidney or muscle, and spleen. The results suggest that these genes could play key roles not only in the ovary but in other female tissues as well.