血管平滑肌细胞的容积调节Cl^-通道生物学特性及功能研究进展

Research Progress on Biological Characteristics and Function of Volume Regulated Cl^- Channel in Vascular Smooth Muscle Cells

血管平滑肌细胞容积调节Cl^-通道(VRCC)通过PI3K/Akt信号通路促进细胞的增殖反应,通过线粒体信号通路保护细胞凋亡,通过JNK/P38/MAPK信号通路促清道夫受体表达和摄取ox-LDL功能增强导致巨噬细胞形成,参与动脉粥样硬化。VRCC通过促进细胞增殖、细胞迁移和外基质积聚,抑制细胞凋亡,参与脑血管重构。VRCC分子基础复杂,至今仍未完全明了。VRCC在不同的细胞和组织是多样性的,而不是一个单一的广泛存在的通道,可由细胞类型和组织特异性亚单位成分组成,在血管平滑肌细胞LRRC8A和ClC-3可能是两个不同的VRCC上的亚单位成分。ClC-3容积调节Cl^-通道受integrin-Src通路使ClC-3上284位酪氨酸磷酸化以及Rho/Rh A-ROCK通路使ClC-3第543位苏氨酸磷酸化两条不同通路调节。

Volume regulated chloride channel（VRCC）enhances cell proliferation through PI3K/Akt signal pathway,andinhibits cell apoptosis through mitochondrial pathway in vascular smooth muscle cells,and accelerates the process of atherosclerosisthrough JNK/p38 MAPK signal pathway,resulting in increasing SR-A expression and ox-LDL uptake.Cerebrovascular remodelingis mediated by VRCC.This effect of VRCC on remodeling is related to accelerating cell proliferation,migration and accumulation of.extracellular matrix.As to the molecular identification of VRCC,it is very complex.VRCC is diversity in various cells or tissues,rather than a single ubiquitous channel,VRCC may be contain variedcell type-or tissue-specific subunitcompositions.ClC-3 volumeregulated Cl-channel is regulated by both integrin-Src and Rho/RhA-Rock signal pathways.