MicroRNA-494-3p Exacerbates Renal Epithelial Cell Dysfunction by Targeting SOCS6 under High Glucose Treatment

• Published in: Kidney & blood pressure research 2022-04, Vol.47 (4), p.247-255
• Main Authors: Xue, Xianjun, Liu, Minjie, Wang, Yulu, Yang, Yanlei, Li, Zhiping, Shi, Ruifang, Miao, Yueting
• Format: Article
• Language: English
• Subjects: Apoptosis; Cell Line; Cell viability; Cholecystokinin; Collagen; Collagen (type I); Collagen (type III); Collagen (type IV); Diabetes mellitus; Diabetic Nephropathies - pathology; Diabetic nephropathy; End-stage renal disease; Epithelial cells; Epithelial Cells - pathology; Epithelium; Fibronectin; Fibrosis; Flow cytometry; Glucose; Glucose - metabolism; Glucose - pharmacology; Humans; Kidney diseases; MicroRNAs - metabolism; miRNA; mRNA; Nephropathy; Polymerase chain reaction; Renal function; Research Article; Suppressor of Cytokine Signaling Proteins - metabolism; Western blotting
• ISSN: 1420-4096; 1423-0143
• DOI: 10.1159/000521647

Background: Diabetic nephropathy is a common complication of the kidneys induced by diabetes and is the main cause of end-stage renal disease. MicroRNA-494-3p was reported to be upregulated in renal tissues collected from db/db mice, but its specific role in diabetic nephropathy was still unclear. This study aimed to explore the effect of miR-494-3p on renal fibrosis using an in vitro cell model of diabetic nephropathy. Methods: After human renal tubular epithelial cells (HK-2) were treated with high glucose (HG), the viability and apoptosis of cells were examined by CCK-8 assays and flow cytometry analyses. Additionally, protein levels of fibronectin, collagen I, collagen III, collagen IV, and epithelial-mesenchymal transition (EMT) markers in HG-induced HK-2 cells were quantified by Western blotting. miR-494-3p expression in HK-2 cells was detected by reverse-transcription quantitative polymerase chain reaction. The binding relation between miR-494-3p and the messenger RNA suppressor of cytokine signaling 6 (SOCS6) was detected by luciferase reporter assays. Results: HG reduced cell viability and enhanced cell apoptosis in a time- or concentration-dependent manner. Additionally, HG induced collagen accumulation and triggered the EMT process. miR-494-3p was upregulated in HG-treated HK-2 cells. miR-494-3p inhibition alleviated HG-induced cell dysfunction. Mechanistically, miR-494-3p bound with SOCS6 and negatively regulated SOCS6 expression. Moreover, silencing SOCS6 rescued the suppressive effect of miR-499-5p inhibition on HG-induced cell dysfunction. Conclusion: miR-494-3p aggravates renal fibrosis, EMT process, and cell apoptosis by targeting SOCS6, suggesting that the miR-494-3p/SOCS6 axis may become a potential strategy for the treatment of diabetic nephropathy.