TRPC6 突变致足细胞病变机制的研究进展

瞬时受体电位阳离子通道蛋白6 (transient channel receptor potential cation 6, TRPC6) 是肾脏足细 胞裂孔隔膜 (slit diaphragm, SD) 的重要组成蛋白之一, 与肌动蛋白、 足细胞表面蛋白以及其他裂孔隔膜 蛋白分子相互作用, 共同维持足细胞的正常功能。 TRPC6 过表达或过度活动导致细胞内钙超载而损伤足细 胞。 目前报道 TRPC6 基因致病突变可导致局灶节段性肾小球硬化症。 近来研究发现, TRPC6 与以蛋白尿为 主要表现的肾小球疾病的发生发展密切相关, 但尚无特效靶向药物应用于临床。 文章主要对 TRPC6 基因突 变致足细胞病变的分子机制以及 TRPC6 基因型与临床表型之间的关系进行了综述。

Advances in Research on Mechanism of TRPC6 Mutation-caused Podocytopathy

Transient channel receptor potential cation 6 (TRPC6) is one of the most essential proteins of the slit diaphragm (SD) on podocytes in the kidney. It interacts with the actin, surface proteins, and other SD components to keep the podocytes functioning normally. The over activation of TRPC6 causes intracellular calcium overload, which injures or destroys podocytes. It is now known that a pathogenic mutation in the TRPC6 gene might cause focal segmental glomerulosclerosis. TRPC6 has been linked to the onset and progression of proteinuric kidney disease in recent researches. However, there is no particular targeted medication for the clinical therapeutics. The molecular mechanisms of podocytes injuries due to TRPC6, as well as the relationship between genetic mutations in TRPC6 and clinical phenotypes are discussed in this review