Department of Nephrology/Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Experimental and Clinical Research Center (ECRC), Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Charité Universitätsmedizin, Berlin, Germany.
Sci Rep. 2022 Feb 22;12(1):3038. doi: 10.1038/s41598-022-06703-9.
Transient receptor potential channel subfamily C, member 6 (TRPC6), a non-selective cation channel that controls influx of Ca and other monovalent cations into cells, is widely expressed in the kidney. TRPC6 gene variations have been linked to chronic kidney disease but its role in acute kidney injury (AKI) is unknown. Here we aimed to investigate the putative role of TRPC6 channels in AKI. We used Trpc6 mice and pharmacological blockade (SH045 and BI-749327), to evaluate short-term AKI outcomes. Here, we demonstrate that neither Trpc6 deficiency nor pharmacological inhibition of TRPC6 influences the short-term outcomes of AKI. Serum markers, renal expression of epithelial damage markers, tubular injury, and renal inflammatory response assessed by the histological analysis were similar in wild-type mice compared to Trpc6 mice as well as in vehicle-treated versus SH045- or BI-749327-treated mice. In addition, we also found no effect of TRPC6 modulation on renal arterial myogenic tone by using blockers to perfuse isolated kidneys. Therefore, we conclude that TRPC6 does not play a role in the acute phase of AKI. Our results may have clinical implications for safety and health of humans with TRPC6 gene variations, with respect to mutated TRPC6 channels in the response of the kidney to acute ischemic stimuli.
瞬时受体电位通道亚家族 C，成员 6（TRPC6），一种非选择性阳离子通道，控制 Ca 和其他单价阳离子流入细胞，在肾脏中广泛表达。TRPC6 基因变异与慢性肾脏病有关，但在急性肾损伤（AKI）中的作用尚不清楚。在这里，我们旨在研究 TRPC6 通道在 AKI 中的潜在作用。我们使用 Trpc6 小鼠和药理学阻断（SH045 和 BI-749327）来评估短期 AKI 结果。在这里，我们证明 Trpc6 缺乏或 TRPC6 的药理学抑制均不影响 AKI 的短期结果。与野生型小鼠相比，血清标志物、上皮损伤标志物的肾脏表达、组织学分析评估的肾小管损伤和肾脏炎症反应在 Trpc6 小鼠中以及在 vehicle 处理与 SH045 或 BI-749327 处理的小鼠中相似。此外，我们还发现 TRPC6 调节对分离肾脏灌注中肾动脉肌源性张力没有影响。因此，我们得出结论，TRPC6 在 AKI 的急性期不起作用。我们的结果可能对具有 TRPC6 基因变异的人类的安全性和健康具有临床意义，因为 TRPC6 通道在肾脏对急性缺血性刺激的反应中发生了突变。
