Department of Laboratory Medicine, Peking University Third Hospital, Haidian District, Beijing, 100191, China.
J Nanosci Nanotechnol. 2021 Feb 1;21(2):1079-1084. doi: 10.1166/jnn.2021.18631.
MicroRNAs are a type of non-coding single-stranded RNA that can mediate target mRNA degradation or inhibit target mRNA translation, thereby regulating target gene expression and have an important role in physiological and pathological processes. At present, miRs have been confirmed to be closely related to kidneys and kidney diseases, and have been involved in the occurrence, development and prognosis of renal fibrosis. Now we review the research progress of miRs in renal fibrosis in recent years, and provide references for the future diagnosis and treatment of renal fibrosis. The incidence of diabetic nephropathy (DN) is increasing year by year, the pathogenesis is complicated, and renal fibrosis occurs during the progress of the disease, which is very difficult to treat. The protein encoded by the PTEN gene has lipid phosphatase and protein phosphatase activity and is the PTEN/AKT and FAK pathway important negative regulators. It can play an anti-fibrotic effect by negatively regulating the PTEN/AKT pathway. Studies show that during the pathogenesis of DN, the expression of PTEN protein is reduced, and the PI3K/AKT pathway is activated to exert multiple fibrotic effects, but affect PTEN. The regulatory factors of expression are still not clear; moreover, the specific mechanism of the decrease in PTEN protein expression in DN pathogenesis. Therefore, this study intends to Intervention of the expression level of miRs in renal tissues, to study its regulation of PTEN and its effect on renal fibrosis, and at the same time, observe the effects on renal tubular epithelial cell phenotype and fibrotic lesions under high glucose conditions by up-regulating and down-regulating PTEN expression. Further elucidate the pathogenesis of DN renal fibrosis, and explore new effective targets for the prevention and treatment of DN.
微小 RNA 是一种非编码的单链 RNA,可以介导靶 mRNA 的降解或抑制靶 mRNA 的翻译,从而调节靶基因的表达,在生理和病理过程中发挥重要作用。目前,miRs 被证实与肾脏和肾脏疾病密切相关,并参与了肾纤维化的发生、发展和预后。现在我们回顾近年来 miRs 在肾纤维化中的研究进展,为肾纤维化的未来诊断和治疗提供参考。糖尿病肾病 (DN) 的发病率逐年上升,发病机制复杂,疾病进展过程中发生肾纤维化,治疗十分困难。PTEN 基因编码的蛋白具有脂质磷酸酶和蛋白磷酸酶活性,是 PTEN/AKT 和 FAK 通路的重要负性调节因子,通过负性调节 PTEN/AKT 通路发挥抗纤维化作用。研究表明,在 DN 的发病机制中,PTEN 蛋白表达减少,PI3K/AKT 通路被激活,发挥多种纤维化作用,但影响 PTEN 表达的调节因子尚不清楚;此外,DN 发病机制中 PTEN 蛋白表达减少的具体机制。因此,本研究拟通过干预肾组织中 miRs 的表达水平,研究其对 PTEN 的调控及其对肾纤维化的影响,并同时观察在高糖条件下通过上调和下调 PTEN 表达对肾小管上皮细胞表型和纤维化病变的影响,进一步阐明 DN 肾纤维化的发病机制,探索防治 DN 的新有效靶点。