Kidney fibrosis is generally confirmed to have a significant role in chronic kidney disease, resulting in end-stage kidney failure. Epithelial–mesenchymal transition (EMT) is an important molecular mechanism contributing to fibrosis. Tubular epithelial cells (TEC), the major component of kidney parenchyma, are vulnerable to different types of injuries and are a significant source of myofibroblast by EMT. Furthermore, TRPC6 knockout plays an anti-fibrotic role in ameliorating kidney damage. However, the relationship between TRPC6 and EMT is unknown. In this study, TRPC6^−/− and wild-type (WT) mice were subjected to a unilateral ureteric obstruction (UUO) operation. Primary TEC were treated with TGF-β1. Western blot and immunofluorescence data showed that fibrotic injuries alleviated with the inhibition of EMT in TRPC6^−/− mice compared to WT mice. The activation of AKT-mTOR and ERK1/2 pathways was down-regulated in the TRPC6^−/− mice, while the loss of Na⁺/K⁺-ATPase and APQ1 was partially recovered. We conclude that TRPC6 knockout may ameliorate kidney fibrosis by inhibition of EMT through down-regulating the AKT-mTOR and ERK1/2 pathways. This could contribute to the development of effective therapeutic strategies on chronic kidney diseases.

通常确认肾脏纤维化在慢性肾脏疾病中具有重要作用，导致终末期肾衰竭。上皮-间质转化（EMT）是导致纤维化的重要分子机制。肾实质的主要组成部分-肾小管上皮细胞（TEC）易受不同类型的伤害，并且是EMT产生肌成纤维细胞的重要来源。此外，TRPC6基因敲除在改善肾脏损害中具有抗纤维化作用。但是，TRPC6和EMT之间的关系是未知的。在这项研究中，TRPC6 ^-/-对野生型（WT）小鼠进行单侧输尿管梗阻（UUO）手术。用TGF-β1治疗原发性TEC。Western印迹和免疫荧光数据表明，与WT小鼠相比，TRPC6 ^-//小鼠的EMT抑制减轻了纤维化损伤。在TRPC6 ^-/-小鼠中，AKT-mTOR和ERK1 / 2途径的激活被下调，而Na ⁺ / K ⁺ -ATPase和APQ1的损失被部分恢复。我们得出的结论是，通过下调AKT-mTOR和ERK1 / 2途径抑制EMT，TRPC6敲除可以改善肾脏纤维化。这可能有助于开发针对慢性肾脏疾病的有效治疗策略。