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miR-485 suppresses inflammation and proliferation of mesangial cells in an in vitro model of diabetic nephropathy by targeting NOX5
Institution:1. Department of General Practice, The First Hospital of China Medical University, Shenyang, China;2. Department of Nephrology, The First Hospital of China Medical University, Shenyang, China;1. Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China;2. Kidney and Dialysis Institute of Shanghai, Shanghai, China;3. Kidney and Blood Purification Laboratory of Shanghai, Shanghai, China;2. Department of Healthcare, Linyi People’s Hospital, Linyi 276000, PR China;3. Department of Image, Linyi People’s Hospital, Linyi 276000, PR China
Abstract:Diabetic nephropathy (DN) is among the common complications of diabetes and is a major cause of end-stage kidney disease. Emerging data indicate that renal inflammation is involved in DN progression and aggravation. Still, the exact cellular mechanisms remain unclear. Dysregulated expression of microRNAs (miRNAs) is associated with multiple diseases, including DN. The relationship between miRNAs and inflammation in DN is also unexplored. Here, we evaluated the role of miR-485 in mediating the response of human mesangial cells (HMCs) to a high glucose (HG) concentration, and the potential underlying mechanism. We found that miR-485 expression is significantly decreased in HG-stimulated HMCs. Overexpression of miR-485 suppressed HG-induced proliferation of HMCs. Lower production of proinflammatory cytokines (i.e., TNF-α, IL-1β, and IL-6) was observed in miR-485–overexpressing HMCs. Overexpression of miR-485 markedly suppressed the overexpression of extracellular-matrix proteins, e.g., collagen IV (Col IV) and fibronectin (FN), in HG-stimulated HMCs. Furthermore, miR-485 suppressed the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 5 (NOX5), restrained the HG-induced HMC proliferation, downregulated the expression of proinflammatory cytokines, and inhibited the production of extracellular-matrix proteins in HMCs. These results provide new insights into the involvement of the miR-485–NOX5 signaling pathway in DN progression.
Keywords:Diabetic nephropathy  miR-485  NOX5  Human mesangial cells  Cell proliferation  Inflammation
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