目的探讨勿动蛋白(Nogo)/Rho相关蛋白激酶(ROCK)-去甲肾上腺素转运蛋白(NET)信号通路对自发性高血压大鼠心肌肥厚与纤维化的调节作用。方法选择7周龄SPF级同源同系雄性自发性高血压大鼠20只,随机分为4组:对照组、Nogo受体拮抗剂(NEP1-40...目的探讨勿动蛋白(Nogo)/Rho相关蛋白激酶(ROCK)-去甲肾上腺素转运蛋白(NET)信号通路对自发性高血压大鼠心肌肥厚与纤维化的调节作用。方法选择7周龄SPF级同源同系雄性自发性高血压大鼠20只,随机分为4组:对照组、Nogo受体拮抗剂(NEP1-40)组、ROCK抑制剂(法舒地尔)组和NET抑制剂(氟西汀)组,每组5只,饲养7周。分离称量左心室质量,计算左心室质量指数。实时定量PCR检测心肌肥厚标志物心钠肽、脑钠肽、β肌球蛋白重链(β-MHC)基因表达,以及心肌纤维化标志物结缔组织生长因子(CTGF)、心肌胶原组织Ⅰ型(CollagenⅠ)、心肌胶原组织Ⅲ型(CollagenⅢ)和NET基因表达水平。结果与对照组比较,NEP1-40组左心室质量指数、心钠肽、脑钠肽、β-MHC表达明显增高,法舒地尔组左心室质量指数、心钠肽、脑钠肽、β-MHC表达明显降低(P<0.05)。与对照组比较,NEP1-40组CTGF、CollagenⅠ、CollagenⅢ表达明显增高,法舒地尔组NET表达明显升高,CTGF、CollagenⅠ、CollagenⅢ和NET表达明显降低(P<0.05)。与对照组比较,氟西汀组心钠肽、脑钠肽、β-MHC、CTGF和CollagenⅠ表达明显增高[(1.37±0.05)%vs (1.26±0.03)%,(1.27±0.04)%vs (1.18±0.07)%,(1.26±0.04)%vs (1.22±0.03)%,2.05±0.01 vs 1.44±0.11,1.86±0.06 vs 1.29±0.05,P<0.05]。结论Nogo/ROCK-NET信号通路参与自发性高血压大鼠心肌肥厚与纤维化的调节。展开更多
A spinal cord injury refers to an injury to the spinal cord that is caused by a trauma instead of diseases. Spinal cord injury includes a primary mechanical injury and a much more complex secondary injury process invo...A spinal cord injury refers to an injury to the spinal cord that is caused by a trauma instead of diseases. Spinal cord injury includes a primary mechanical injury and a much more complex secondary injury process involving inflammation, oxidation, excitotoxicity, and cell death. During the secondary injury, many signal pathways are activated and play important roles in mediating the pathogenesis of spinal cord injury. Among them, the Rho A/Rho kinase pathway plays a particular role in mediating spinal degeneration and regeneration. In this review, we will discuss the role and mechanism of Rho A/Rho kinase-mediated spinal cord pathogenesis, as well as the potential of targeting Rho A/Rho kinase as a strategy for promoting both neuroprotection and axonal regeneration.展开更多
Previous studies show that actin-binding Rho activating protein （Abra） is expressed in cardiomyocytes and vascular smooth muscle cells. In this study, we investigated the expression profile of Abra in the central ne...Previous studies show that actin-binding Rho activating protein （Abra） is expressed in cardiomyocytes and vascular smooth muscle cells. In this study, we investigated the expression profile of Abra in the central nervous system of normal adult rats by confocal immunofluorescence. Results showed that Abra immunostaining was located in neuronal nuclei, cytoplasm and processes in the central nervous system, with the strongest staining in the nuclei; in the cerebral cortex, Abra positive neuronal bodies and processes were distributed in six cortical layers including molecular layer, external granular layer, external pyramidal layer, internal granular layer, internal pyramidal layer and polymorphic layer; in the hippocampus, the cell bodies of Abra positive neurons were distributed evenly in pyramidal layer and granular layer, with positive processes in molecular layer and orien layer; in the cerebellar cortex, Abra staining showed the positive neuronal cell bodies in Purkinje cell layer and granular layer and positive processes in molecular layer; in the spinal cord, Abra-immunopositive products covered the whole gray matter and white matter; co-localization studies showed that Abra was co-stained with F-actin in neuronal cytoplasm and processes, but weakly in the nuclei. In addition, in the hippocampus, Abra was co-stained with F-actin only in neuronal processes, but not in the cell body. This study for the first time presents a comprehensive overview of Abra expression in the central nervous system, providing insights for further investigating the role of Abra in the mature central nervous system.展开更多
Neurons are highly polarized cells with a single long axon and multiple dendrites, all of which are actinrich structures. The precise regulation of neuronal cell morphology is a fundamental aspect of neurobiology. The...Neurons are highly polarized cells with a single long axon and multiple dendrites, all of which are actinrich structures. The precise regulation of neuronal cell morphology is a fundamental aspect of neurobiology. The major role of Rho GTPases, which is conserved in all eukaryotes, is to regulate the actin and microtubule cytoskeleton. Therefore theRhoGTPases are key regulators of neuronal morphology during development besides their canonical functions in actin cytoskeletal regulation, cell migration and cell cycle progression. Semaphorins are a family of secreted or transmembrane proteins, which function through their receptor plexins and/or neuropilins to act as the repulsive or attractive guidance cues for axons and dendrites. It has been demonstrated that the fully activetion of plexins appears to be dependent on the binding of RhoGTPases to theRhobinding domain (RBD) and Semaphorin to the extracellular region. Here, we summarize the functions of the small Rho GTPases in two well-studied vertebrate Semaphorins, Sema3Aand Sema4D;and the potential roles of the small Rho GTPases in some poorly-studied vertebrate Semaphorins Sema5A, Sema6Aand Sema7A. We also summarize the functions of different members of Ras family, R-Ras, M-Ras and Rap, in Semaphorin signalling pathways as well.展开更多
The published article titled“MicroRNA-148a Acts as a Tumor Suppressor in Osteosarcoma via Targeting Rho-Associated Coiled-Coil Kinase”has been retracted from Oncology Research,Vol.25,No.8,2017,pp.1231–1243.DOI:10.3...The published article titled“MicroRNA-148a Acts as a Tumor Suppressor in Osteosarcoma via Targeting Rho-Associated Coiled-Coil Kinase”has been retracted from Oncology Research,Vol.25,No.8,2017,pp.1231–1243.DOI:10.3727/096504017X14850134190255 URL:https://www.techscience.com/or/v25n8/56908 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.展开更多
文摘目的探讨勿动蛋白(Nogo)/Rho相关蛋白激酶(ROCK)-去甲肾上腺素转运蛋白(NET)信号通路对自发性高血压大鼠心肌肥厚与纤维化的调节作用。方法选择7周龄SPF级同源同系雄性自发性高血压大鼠20只,随机分为4组:对照组、Nogo受体拮抗剂(NEP1-40)组、ROCK抑制剂(法舒地尔)组和NET抑制剂(氟西汀)组,每组5只,饲养7周。分离称量左心室质量,计算左心室质量指数。实时定量PCR检测心肌肥厚标志物心钠肽、脑钠肽、β肌球蛋白重链(β-MHC)基因表达,以及心肌纤维化标志物结缔组织生长因子(CTGF)、心肌胶原组织Ⅰ型(CollagenⅠ)、心肌胶原组织Ⅲ型(CollagenⅢ)和NET基因表达水平。结果与对照组比较,NEP1-40组左心室质量指数、心钠肽、脑钠肽、β-MHC表达明显增高,法舒地尔组左心室质量指数、心钠肽、脑钠肽、β-MHC表达明显降低(P<0.05)。与对照组比较,NEP1-40组CTGF、CollagenⅠ、CollagenⅢ表达明显增高,法舒地尔组NET表达明显升高,CTGF、CollagenⅠ、CollagenⅢ和NET表达明显降低(P<0.05)。与对照组比较,氟西汀组心钠肽、脑钠肽、β-MHC、CTGF和CollagenⅠ表达明显增高[(1.37±0.05)%vs (1.26±0.03)%,(1.27±0.04)%vs (1.18±0.07)%,(1.26±0.04)%vs (1.22±0.03)%,2.05±0.01 vs 1.44±0.11,1.86±0.06 vs 1.29±0.05,P<0.05]。结论Nogo/ROCK-NET信号通路参与自发性高血压大鼠心肌肥厚与纤维化的调节。
基金supported by NIH NS050243,NS059622,NS073636,DOD CDMRP W81XWH-12-1-0562,DVA 1I01BX002356-01A1Craig H Neilsen Foundation#296749+2 种基金Wallace H.Coulter FoundationIndiana Spinal Cord and Brain Injury Research FoundationMari Hulman George Endowment Funds
文摘A spinal cord injury refers to an injury to the spinal cord that is caused by a trauma instead of diseases. Spinal cord injury includes a primary mechanical injury and a much more complex secondary injury process involving inflammation, oxidation, excitotoxicity, and cell death. During the secondary injury, many signal pathways are activated and play important roles in mediating the pathogenesis of spinal cord injury. Among them, the Rho A/Rho kinase pathway plays a particular role in mediating spinal degeneration and regeneration. In this review, we will discuss the role and mechanism of Rho A/Rho kinase-mediated spinal cord pathogenesis, as well as the potential of targeting Rho A/Rho kinase as a strategy for promoting both neuroprotection and axonal regeneration.
基金supported by the National Natural Science Foundation of China,No.30971532Ph.D.Programs Foundation of Ministry of Education of China,No.20090162110063+1 种基金the Natural Science Foundation of Hunan Province,No.09JJ5015the Scientific Research Program of Hunan Provincial Higher Education Institutes,No.110541
文摘Previous studies show that actin-binding Rho activating protein （Abra） is expressed in cardiomyocytes and vascular smooth muscle cells. In this study, we investigated the expression profile of Abra in the central nervous system of normal adult rats by confocal immunofluorescence. Results showed that Abra immunostaining was located in neuronal nuclei, cytoplasm and processes in the central nervous system, with the strongest staining in the nuclei; in the cerebral cortex, Abra positive neuronal bodies and processes were distributed in six cortical layers including molecular layer, external granular layer, external pyramidal layer, internal granular layer, internal pyramidal layer and polymorphic layer; in the hippocampus, the cell bodies of Abra positive neurons were distributed evenly in pyramidal layer and granular layer, with positive processes in molecular layer and orien layer; in the cerebellar cortex, Abra staining showed the positive neuronal cell bodies in Purkinje cell layer and granular layer and positive processes in molecular layer; in the spinal cord, Abra-immunopositive products covered the whole gray matter and white matter; co-localization studies showed that Abra was co-stained with F-actin in neuronal cytoplasm and processes, but weakly in the nuclei. In addition, in the hippocampus, Abra was co-stained with F-actin only in neuronal processes, but not in the cell body. This study for the first time presents a comprehensive overview of Abra expression in the central nervous system, providing insights for further investigating the role of Abra in the mature central nervous system.
文摘Neurons are highly polarized cells with a single long axon and multiple dendrites, all of which are actinrich structures. The precise regulation of neuronal cell morphology is a fundamental aspect of neurobiology. The major role of Rho GTPases, which is conserved in all eukaryotes, is to regulate the actin and microtubule cytoskeleton. Therefore theRhoGTPases are key regulators of neuronal morphology during development besides their canonical functions in actin cytoskeletal regulation, cell migration and cell cycle progression. Semaphorins are a family of secreted or transmembrane proteins, which function through their receptor plexins and/or neuropilins to act as the repulsive or attractive guidance cues for axons and dendrites. It has been demonstrated that the fully activetion of plexins appears to be dependent on the binding of RhoGTPases to theRhobinding domain (RBD) and Semaphorin to the extracellular region. Here, we summarize the functions of the small Rho GTPases in two well-studied vertebrate Semaphorins, Sema3Aand Sema4D;and the potential roles of the small Rho GTPases in some poorly-studied vertebrate Semaphorins Sema5A, Sema6Aand Sema7A. We also summarize the functions of different members of Ras family, R-Ras, M-Ras and Rap, in Semaphorin signalling pathways as well.
文摘The published article titled“MicroRNA-148a Acts as a Tumor Suppressor in Osteosarcoma via Targeting Rho-Associated Coiled-Coil Kinase”has been retracted from Oncology Research,Vol.25,No.8,2017,pp.1231–1243.DOI:10.3727/096504017X14850134190255 URL:https://www.techscience.com/or/v25n8/56908 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.
