Hyperglycemia-Induced miR-155 Amplifies Inflammatory Cytokine Secretion in Human Mesangial Cells via SOCS1 Suppression

Abstract

Background:
Diabetic nephropathy is characterized by chronic low-grade inflammation within renal tissues. MicroRNA-155 (miR-155) is a key regulator of inflammatory cascades; however, its role in mesangial cell injury under hyperglycemic conditions requires clarification.
Objectives: To evaluate miR-155 expression and its effect on pro-inflammatory cytokine secretion in cultured human mesangial cells exposed to high glucose concentrations.
Materials and methods: Primary human mesangial cells were cultured under normal (5.5 mM) or high (25 mM) D-glucose conditions. Expression of miR-155 was quantified using quantitative real-time RT-PCR. Cells were transfected with miR-155 mimics or inhibitors, and secretion of IL-6, TNF-α, and MCP-1 was measured by ELISA.
Results: High glucose exposure increased miR-155 expression in mesangial cells 3.8-fold compared with normal glucose controls (p < 0.001). Transfection with a miR-155 inhibitor under high glucose conditions significantly decreased the secretion of IL-6 (by 48.5%), TNF-α (by 52.1%), and MCP-1 (by 41.0%; p < 0.001). Mechanistic analyses confirmed that miR-155 directly targets suppressor of cytokine signaling 1 (SOCS1), thereby activating NF-κB signaling.
Conclusions: Hyperglycemia upregulates miR-155 expression, which amplifies inflammatory responses in human mesangial cells via SOCS1 suppression, highlighting miR-155 as a potential therapeutic target in diabetic nephropathy.

Keywords:
MicroRNA-155; miR-155; diabetic nephropathy; mesangial cells; hyperglycemia; SOCS1.