MiR-194 targets Runx1/Akt pathway to reduce renal fibrosis in mice with unilateral ureteral obstruction
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NEPHROLOGY - ORIGINAL PAPER
MiR‑194 targets Runx1/Akt pathway to reduce renal fibrosis in mice with unilateral ureteral obstruction Li Cheng1 · Can Tu1 · Yonglong Min1 · Da He1 · Sheng Wan1 · Fei Xiong1 Received: 25 March 2020 / Accepted: 15 June 2020 © Springer Nature B.V. 2020
Abstract Purpose Chronic kidney disease (CKD) has become a global public health problem and accompanied by renal fibrosis. MiR-194, a tumor suppressor gene, has been previously reported to be associated with the pathogenesis of tissue fibrosis. However, the role of miR-194 in the pathogenesis of renal fibrosis remains unknown. Methods A renal fibrosis model was constructed by unilateral ureteral obstruction (UUO) in male C57BL/6 mice. HE and MASSON stainings were used for histological analysis. The expression level of miR-194 was detected by RT-qPCR. The protein expression was detected by western blotting. The levels of inflammatory cytokines were detected by ELISA. The relationship between miR-194 and Runx1 was further verified by dual luciferase reporter assay. Results The results showed that miR-194 level was downregulated in kidney tissue of UUO mice, accompanied by significantly pathological damage and renal fibrosis. MiR-194 mimics significantly reduced pathological damage and alleviated renal fibrosis that caused by UOO, and inhibited the expression levels of α-SMA and collagen I. In addition, miR-194 mimics also reduced the expression level of serum inflammatory factors. Moreover, in vitro analysis indicated that Runx1 was a downstream target gene of miR-194. Furthermore, mechanism analysis indicated that miR-194 reduced mouse renal fibrosis by inhibiting the Runx1/AKT pathway in vivo and in vitro. Conclusion The present findings suggested that miR-194 targets Runx1/Akt pathway to reduce renal fibrosis in UOO-induced mice. This study provides a novel strategy for the prevention and treatment of renal fibrosis. Keywords miR-194 · Renal fibrosis · Inflammation · Runt-related transcription factor 1 · Protein kinase B Abbreviations CKD Chronic kidney disease UUO Unilateral ureteral obstruction
Background Chronic kidney disease (CKD) has become a global public health problem, often accompanied by renal inflammation and fibrotic lesions. The prevalence of CKD has increased year by year worldwide, and is 11–13% in China. It is worth noting that renal tubular epithelial cells contribute to renal fibrosis through epithelial–mesenchymal transition in inflammation [1–4]. In general, renal fibrosis is the principal process underlying the progression of CKD [5]. Therefore, it * Fei Xiong [email protected] 1
Department of Nephrology, Hubei Province, Wuhan No. 1 Hospital, 215# Zhongshan Avenue, Wuhan 430022, China
is of great significance to explore the mechanism underlying renal fibrosis for the prevention and treatment of end-stage renal failure. MicroRNA (20–22 nt) has been recognized as important regulators for various diseases and malignant tumorigenesis [6, 7]. For example, miR-194 was associated with larger tumor size (≥ 4
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