Department of Medicine, Rush University Medical Center, Chicago, Illinois, USA; Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, USA.
Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Kidney Int. 2023 Jun;103(6):1056-1062. doi: 10.1016/j.kint.2023.01.016. Epub 2023 Feb 5.
Transient receptor potential canonical channels (TRPCs) are non-selective cationic channels that play a role in signal transduction, especially in G -protein-mediated signaling cascades. TRPC5 is expressed predominantly in the brain but also in the kidney. However, its role in kidney physiology and pathophysiology is controversial. Some studies have suggested that TRPC5 drives podocyte injury and proteinuria, particularly after small GTPase Rac1 activation to induce the trafficking of TRPC5 to the plasma membrane. Other studies using TRPC5 gain-of-function transgenic mice have questioned the pathogenic role of TRPC5 in podocytes. Here, we show that TRPC5 over-expression or inhibition does not ameliorate proteinuria induced by the expression of constitutively active Rac1 in podocytes. Additionally, single-cell patch-clamp studies did not detect functional TRPC5 channels in primary cultures of podocytes. Thus, we conclude that TRPC5 plays a role redundant to that of TRPC6 in podocytes and is unlikely to be a useful therapeutic target for podocytopathies.
瞬时受体电位经典通道（TRPC）是非选择性阳离子通道，在信号转导中发挥作用，特别是在 G 蛋白介导的信号级联反应中。TRPC5 主要在大脑中表达，但也在肾脏中表达。然而，它在肾脏生理学和病理生理学中的作用存在争议。一些研究表明，TRPC5 驱动足细胞损伤和蛋白尿，特别是在小 GTP 酶 Rac1 激活后，诱导 TRPC5 向质膜转运。使用 TRPC5 功能获得性转基因小鼠的其他研究对 TRPC5 在足细胞中的致病作用提出了质疑。在这里，我们表明，TRPC5 的过表达或抑制不能改善足细胞中组成性激活 Rac1 表达诱导的蛋白尿。此外，单细胞膜片钳研究未在足细胞的原代培养物中检测到功能性 TRPC5 通道。因此，我们得出结论，TRPC5 在足细胞中的作用与 TRPC6 冗余，不太可能成为足细胞病的有用治疗靶点。
