Bai Lin, Lin Yongtao, Xie Juan, Zhang Yiyuan, Wang Hongwu, Zheng Donghui
Department of Nephrology, Affiliated Huai'an Hospital of Xuzhou Medical University, 62# Huaihai South Road, Huai'an, 223001, Jiangsu, People's Republic of China.
Xuzhou Medical University, Xuzhou, 221004, Jiangsu, People's Republic of China.
Hum Cell. 2021 Mar;34(2):383-393. doi: 10.1007/s13577-020-00474-z. Epub 2021 Jan 17.
Renal fibrosis is a pathologic change in chronic kidney disease (CKD). MicroRNAs (miRNAs) have been shown to play an important role in the development of renal fibrosis. However, the biological role of miR-27b-3p in renal fibrosis remains unclear. Thus, this study aimed to investigate the role of miR-27b-3p in the progression of renal fibrosis. In this study, HK-2 cells were stimulated with transforming growth factor (TGF)-β1 for mimicking fibrosis progression in vitro. The unilateral ureteric obstruction (UUO)-induced mice renal fibrosis in vivo was established as well. The results indicated that the overexpression of miR-27b-3p significantly inhibited epithelial-to-mesenchymal transition (EMT) in TGF-β1-stimulated HK-2 cells, as shown by the decreased expressions of α-SMA, collagen III, Fibronectin and Vimentin. In addition, overexpression of miR-27b-3p markedly decreased TGF-β1-induced apoptosis in HK-2 cells, as evidenced by the decreased levels of Fas, active caspase 8 and active caspase 3. Meanwhile, dual-luciferase assay showed that miR-27b-3p downregulated signal transducers and activators of transcription 1 (STAT1) expression through direct binding with the 3'-UTR of STAT1. Furthermore, overexpression of miR-27b-3p attenuated UUO-induced renal fibrosis via downregulation of STAT1, α-SMA and collagen III. In conclusion, miR-27b-3p overexpression could alleviate renal fibrosis via suppressing STAT1 in vivo and in vitro. Therefore, miR-27b-3p might be a promising therapeutic target for the treatment of renal fibrosis.
肾纤维化是慢性肾脏病（CKD）中的一种病理变化。微小RNA（miRNA）已被证明在肾纤维化的发展中起重要作用。然而，miR-27b-3p在肾纤维化中的生物学作用仍不清楚。因此，本研究旨在探讨miR-27b-3p在肾纤维化进展中的作用。在本研究中，用转化生长因子（TGF）-β1刺激HK-2细胞以在体外模拟纤维化进展。还建立了单侧输尿管梗阻（UUO）诱导的小鼠体内肾纤维化模型。结果表明，miR-27b-3p的过表达显著抑制了TGF-β1刺激的HK-2细胞中的上皮-间质转化（EMT），α-SMA、III型胶原、纤连蛋白和波形蛋白的表达降低表明了这一点。此外，miR-27b-3p的过表达显著降低了TGF-β1诱导的HK-2细胞凋亡，Fas、活性半胱天冬酶8和活性半胱天冬酶3水平降低证明了这一点。同时，双荧光素酶测定表明，miR-27b-3p通过与STAT1的3'-UTR直接结合下调信号转导和转录激活因子1（STAT1）的表达。此外，miR-27b-3p的过表达通过下调STAT1、α-SMA和III型胶原减轻了UUO诱导的肾纤维化。总之，miR-27b-3p过表达可通过在体内和体外抑制STAT1来减轻肾纤维化。因此，miR-27b-3p可能是治疗肾纤维化的一个有前景的治疗靶点。
