瞬时受体电位规范6(TRPC6)通道,允许Ca2+通过的非选择性阳离子通道,在肾脏疾病中起着重要作用。TRPC6被Ca2+内流激活,氧化应激,和机械应力。研究表明,除了肾小球疾病,TRPC6可导致肾小管疾病,如急性肾损伤,肾间质纤维化,和肾细胞癌(RCC)。然而,TRPC6的小管特异性生理功能尚未阐明。其在缺血/再灌注(I/R)损伤中的病理生理作用尚有争议。因此,TRPC6在I/R损伤中可能具有双重作用。在单侧输尿管梗阻(UUO)小鼠模型中,TRPC6诱导肾纤维化和免疫细胞浸润。此外,TRPC6过表达可能会改变G2相变,从而改变DNA损伤检查点,这可能导致基因组不稳定和RCC肿瘤发生,并可以控制RCC细胞的增殖。这篇综述强调了TRPC6在肾小管系统各种情况下的重要性。为了更好地了解某些肾脏疾病,并最终确定新的治疗目标以改善患者护理,必须阐明TRPC6的病理生理学。
The transient receptor potential canonical 6 (TRPC6) channel, a nonselective cation channel that allows the passage of Ca2+, plays an important role in renal diseases. TRPC6 is activated by Ca2+ 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.