Kidney & Blood Pressure Research (Jan 2022)

MicroRNA-494-3p exacerbates renal epithelial cell dysfunction by targeting SOCS6 under high glucose treatment

  • Xianjun Xue,
  • Minjie Liu,
  • Yulu Wang,
  • Yanlei Yang,
  • Zhiping Li,
  • Ruifang Shi,
  • Yueting Miao

DOI
https://doi.org/10.1159/000521647

Abstract

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Background: Diabetic nephropathy is a common complication of 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.