Department of Nephrology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Ren Fail. 2024 Dec;46(2):2376929. doi: 10.1080/0886022X.2024.2376929. Epub 2024 Jul 18.
The transient receptor potential canonical 6 (TRPC6) channel, a nonselective cation channel that allows the passage of Ca, plays an important role in renal diseases. TRPC6 is activated by Ca influx, oxidative stress, and mechanical stress. Studies have shown that in addition to glomerular diseases, TRPC6 can contribute to renal tubular disorders, such as acute kidney injury, renal interstitial fibrosis, and renal cell carcinoma (RCC). However, the tubule-specific physiological functions of TRPC6 have not yet been elucidated. Its pathophysiological role in ischemia/reperfusion (I/R) injury is debatable. Thus, TRPC6 may have dual roles in I/R injury. TRPC6 induces renal fibrosis and immune cell infiltration in a unilateral ureteral obstruction (UUO) mouse model. Additionally, TRPC6 overexpression may modify G2 phase transition, thus altering the DNA damage checkpoint, which can cause genomic instability and RCC tumorigenesis and can control the proliferation of RCC cells. This review highlights the importance of TRPC6 in various conditions of the renal tubular system. To better understand certain renal disorders and ultimately identify new therapeutic targets to improve patient care, the pathophysiology of TRPC6 must be clarified.
瞬时受体电位经典型 6（TRPC6）通道是一种非选择性阳离子通道，允许 Ca 通过，在肾脏疾病中发挥重要作用。TRPC6 可被 Ca 内流、氧化应激和机械应激激活。研究表明，除了肾小球疾病外，TRPC6 还可能导致肾小管疾病，如急性肾损伤、肾间质纤维化和肾细胞癌（RCC）。然而，TRPC6 在肾小管中的生理功能尚未阐明。其在缺血/再灌注（I/R）损伤中的病理生理作用仍存在争议。因此，TRPC6 在 I/R 损伤中可能具有双重作用。TRPC6 在单侧输尿管梗阻（UUO）小鼠模型中诱导肾纤维化和免疫细胞浸润。此外，TRPC6 过表达可能改变 G2 期过渡，从而改变 DNA 损伤检查点，导致基因组不稳定和 RCC 肿瘤发生，并控制 RCC 细胞的增殖。本综述强调了 TRPC6 在肾脏管状系统各种情况下的重要性。为了更好地理解某些肾脏疾病，并最终确定改善患者治疗的新治疗靶点，必须阐明 TRPC6 的病理生理学。
