MiR-203 improved renal cell injury in diabetic nephropathy by targeting SOCS6/SOCS7 and inhibiting JAK/STAT pathway activation

This study investigates the role of miR-203 in regulating renal cell injury in diabetic nephropathy by targeting the suppressor of cytokine signaling (SOCS) proteins SOCS6 and SOCS7. Using NRK cells, we assessed apoptosis through flow cytometry and TUNEL assays, while real-time quantitative PCR (RT-PCR) quantified miRNA and mRNA expressions. Cell viability was measured using the CCK-8 assay, and cytokine levels were determined through ELISA. We also evaluated reactive oxygen species (ROS) and malondialdehyde (MDA) levels with specific assay kits. The dual luciferase assay confirmed the interaction of miR-203 with SOCS6 and SOCS7. Western blotting analyzed the protein levels of key signaling molecules including JAK1, p-JAK1, JAK2, p-JAK2, STAT3, and p-STAT3.Our findings revealed that high glucose (HG) treatment reduced miR-203 levels, leading to decreased NRK cell proliferation, increased cytokine concentrations (TNF-alpha, IL-1 beta, IL-4, IL-6), heightened ROS and MDA levels, and increased cell apoptosis. Notably, miR-203 mimics counteracted HG's detrimental effects, while miR-203 inhibitors exacerbated them. Mechanistically, miR-203 directly decreased SOCS6 and SOCS7 expression, thereby inhibiting JAK/STAT3 signaling. Thus, miR-203 provides protective effects against renal cell injury by modulating SOCS and their associated pathways.