Department of Nephrology, the First Hospital of Jilin University, China.
Department of Andrology, the First Hospital of Jilin University, China.
Gene. 2020 Jan 10;723:143986. doi: 10.1016/j.gene.2019.143986. Epub 2019 Jul 16.
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Accumulating evidence shows that microRNAs play important roles in diabetic kidney. However, the potential role of MicroRNA-544 (miR-544) in DN remains unclear. In this study, we explored the role of miR-544 on inflammation and fibrosis in diabetic kidney using db/db mice. Renal expression of miR-544 was decreased in mice, companied by increased the expression of FASN. The dual luciferase assay confirmed FASN as a direct target of miR-544. Over-expression of miR-544 significantly ameliorated renal injury, mesangial matrix and renal fibrosis. In addition, over-expression of miR-544 significantly attenuated inflammatory cells infiltration and IL-1, IL-6, TNF- and iNOS production in DN. Furthermore, miR-544 over-expression inhibited the activation of NF-kB signal pathway in DN. In conclusion, our finding demonstrated that miR-544 attenuates diabetic renal injury via suppressing glomerulosclerosis and inflammation by targeting FASN, suggesting that miR-544 might have therapeutic potential for the treatment of DN.
糖尿病肾病（DN）是终末期肾病的主要原因。越来越多的证据表明，microRNAs 在糖尿病肾脏中发挥重要作用。然而，MicroRNA-544（miR-544）在 DN 中的潜在作用尚不清楚。在这项研究中，我们使用 db/db 小鼠探讨了 miR-544 对糖尿病肾脏中炎症和纤维化的作用。miR-544 在小鼠中的表达降低，同时 FASN 的表达增加。双荧光素酶报告实验证实 FASN 是 miR-544 的直接靶标。miR-544 的过表达显著改善了肾脏损伤、肾小球系膜基质和肾脏纤维化。此外，miR-544 的过表达显著减轻了 DN 中炎性细胞浸润以及 IL-1、IL-6、TNF-α 和 iNOS 的产生。此外，miR-544 的过表达抑制了 DN 中 NF-κB 信号通路的激活。总之，我们的研究结果表明，miR-544 通过靶向 FASN 抑制肾小球硬化和炎症来减轻糖尿病肾脏损伤，提示 miR-544 可能具有治疗 DN 的潜力。
