State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China.
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China.
Toxicol Appl Pharmacol. 2021 Jun 1;420:115530. doi: 10.1016/j.taap.2021.115530. Epub 2021 Apr 13.
Chronic Kidney Disease (CKD) is a serious threat to human health. In addition, kidney fibrosis is a key pathogenic intermediate for the progression of CDK. Moreover, excessive activation of fibroblasts is key to the development of kidney fibrosis and this process is difficult to control. Notably, fraxinellone is a natural compound isolated from Dictamnus dasycarpus and has a variety of pharmacological activities, including hepatoprotective, anti-inflammatory and anti-cancer effects. However, the effect of fraxinellone on kidney fibrosis is largely unknown. The present study showed that fraxinellone could alleviate folic acid-induced kidney fibrosis in mice in a dose dependent manner. Additionally, the results revealed that fraxinellone could effectively down-regulate the expression of CUGBP1, which was highly up-regulated in human and murine fibrotic renal tissues. Furthermore, expression of CUGBP1 was selectively induced by the Transforming Growth Factor-beta (TGF-β) through p38 and JNK signaling in kidney fibroblasts. On the other hand, downregulating the expression of CUGBP1 significantly inhibited the activation of kidney fibroblasts. In conclusion, these findings demonstrated that fraxinellone might be a new drug candidate and CUGBP1 could be a promising target for the treatment of kidney fibrosis.
慢性肾脏病（CKD）是对人类健康的严重威胁。此外，肾纤维化是 CKD 进展的关键致病中间环节。此外，成纤维细胞的过度激活是肾纤维化发展的关键，这一过程难以控制。值得注意的是，蛇床子素是从蛇床中分离得到的一种天然化合物，具有多种药理活性，包括保肝、抗炎和抗癌作用。然而，蛇床子素对肾纤维化的作用在很大程度上是未知的。本研究表明，蛇床子素可在一定程度上减轻叶酸诱导的小鼠肾纤维化。此外，结果表明，蛇床子素可有效下调 CUGBP1 的表达，CUGBP1 在人类和鼠类纤维化肾组织中高度上调。此外，转化生长因子-β（TGF-β）通过 p38 和 JNK 信号通路在肾成纤维细胞中选择性诱导 CUGBP1 的表达。另一方面，下调 CUGBP1 的表达可显著抑制肾成纤维细胞的激活。综上所述，这些发现表明蛇床子素可能是一种新的药物候选物，而 CUGBP1 可能是治疗肾纤维化的有前途的靶点。
