Diabetic cardiomyopathy (DCM) is one of the main causes of heart failure in patients with diabetes. Cardiac fibrosis caused by endothelial mesenchymal transformation (EndMT) plays an important role in the pathogenesis of DCM. NLRC5 is a recently discovered immune and inflammatory regulatory molecule in the NOD-like receptor family, and is involved in organ fibrosis. In this study, we found that the expression of NLRC5 was up-regulated in endothelial cells (ECs) and cardiac fibroblasts (CFs) in diabetes models both in vivo and in vitro. NLRC5 knockdown significantly inhibited high glucose-induced EndMT. In addition, NLRC5 deficiency inhibited the expression of phosphorylated Smad2/3 and the activation of EndMT-related transcription factors in ECs induced by high glucose. However, the effect of NLRC5 deficiency on CFs was not obvious. In summary, our results suggest that NLRC5 deficiency ameliorates cardiac fibrosis in DCM by inhibiting EndMT through Smad2/3 signaling pathway and related transcription factors. NLRC5 is likely to be a biomarker and therapeutic target of cardiac fibrosis in diabetic cardiomyopathy.

糖尿病性心肌病（DCM）是糖尿病患者心力衰竭的主要原因之一。内皮间质转化（EndMT）引起的心脏纤维化在DCM的发病机制中起着重要作用。NLRC5是NOD样受体家族中最近发现的免疫和炎症调节分子，参与器官纤维化。在这项研究中，我们发现在体内和体外的糖尿病模型中，内皮细胞（ECs）和心脏成纤维细胞（CFs）中NLRC5的表达均上调。NLRC5基因敲低显着抑制了高糖诱导的EndMT。此外，NLRC5缺乏抑制高糖诱导的EC中磷酸化Smad2 / 3的表达和EndMT相关转录因子的激活。但是，NLRC5缺乏对CF的影响并不明显。综上所述，我们的结果表明，NLRC5缺乏症通过通过Smad2 / 3信号通路和相关转录因子抑制EndMT改善了DCM中的心脏纤维化。NLRC5可能是糖尿病性心肌病中心脏纤维化的生物标志物和治疗靶标。