Hou Yi, Zhang Yan, Lin Sitong, Yu Yue, Yang Liu, Li Lei, Wang Wenxiang
Department of Urology, China-Japan Union Hospital of Jilin University Changchun 130033, Jilin, P. R. China.
Department of Endocrinology, China-Japan Union Hospital of Jilin University Changchun 130033, Jilin, P. R. China.
Am J Transl Res. 2021 Apr 15;13(4):2006-2020. eCollection 2021.
Apigenin (APG), a natural flavonoid with anti-inflammatory and anti-fibrosis properties, has been shown to play a protective role in diabetic nephropathy (DN), but their molecular protection mechanism for miRNA has not been elucidated in detail. This study was designed to focus on exploring its protective role in DN and whether miR-423-5p-upstream stimulating factor 2 (USF2) axis was involved in its protective mechanism. The in vivo model of rat was induced by streptozotocin (STZ) and the in vitro model of renal tubular epithelial cell (RTEC) was induced by high glucose (HG). Our in vivo study revealed that APG had different protective effects on inflammation, renal fibrosis and epithelial mesenchymal transition (EMT) in DN rats, which is mainly reflected in that the inflammatory factors (IL-6, IFN-γ, TNF-α) were obviously down-regulated, the renal fibrosis markers (IV-C, FN, Col I) were significantly inhibited, the E-cadherin (EMT factors) was significantly up-regulated, while the vimentin and α-SMA (EMT factors) were significantly down-regulated, and the renal function indexes (serum Cr, BUN) were significantly improved. In terms of mechanism, the protective effect of APG was related to the regulation of the expression of miR-423-5p-USF2 axis, and there was a targeted relationship between miR-423-5p and USF2. Down-regulating miR-423-5p or up-regulating USF2 could significantly aggravate the disease progression of in vitro model and eliminate DN resistance under APG intervention. The above results revealed that the protective role of APG on DN was mediated by miR-423-5p-USF2 axis.
芹菜素（APG）是一种具有抗炎和抗纤维化特性的天然黄酮类化合物，已被证明在糖尿病肾病（DN）中发挥保护作用，但其对微小RNA（miRNA）的分子保护机制尚未详细阐明。本研究旨在探讨其在DN中的保护作用，以及miR-423-5p-上游刺激因子2（USF2）轴是否参与其保护机制。大鼠体内模型由链脲佐菌素（STZ）诱导，肾小管上皮细胞（RTEC）体外模型由高糖（HG）诱导。我们的体内研究表明，APG对DN大鼠的炎症、肾纤维化和上皮-间质转化（EMT）具有不同的保护作用，主要表现为炎症因子（IL-6、IFN-γ、TNF-α）明显下调，肾纤维化标志物（IV-C、FN、Col I）显著受到抑制，E-钙黏蛋白（EMT因子）显著上调，而波形蛋白和α-平滑肌肌动蛋白（α-SMA，EMT因子）显著下调，并且肾功能指标（血清Cr、BUN）显著改善。在机制方面，APG的保护作用与miR-423-5p-USF2轴表达的调节有关，且miR-423-5p与USF2之间存在靶向关系。下调miR-423-5p或上调USF2可显著加重体外模型的疾病进展，并消除APG干预下的DN抗性。上述结果表明，APG对DN的保护作用是由miR-423-5p-USF2轴介导的。
