Alpha-lipoic acid could attenuate the effect of chemerin-induced diabetic nephropathy progression

Objective(s): Chemerin is associated with insulin resistance, obesity, and metabolic syndrome. α-lipoic acid (α-LA) is a potent antioxidant involved in the reduction of diabetic symptoms. This study aimed to investigate the relationship between chemerin and P۳۸ MAPK in the progression of diabetic nephropathy (DN) and examine the effects of α-LA on chemerin-treated human mesangial cells (HMCs). Materials and Methods: HMCs were transfected with a chemerin-overexpressing plasmid. HMCs were also treated with high-glucose, chemerin, α-LA, PDTC (pyrrolidine dithiocarbamate ammonium, NF-κB p۶۵ inhibitor), and/or SB۲۰۳۵۸۰ (P۳۸ MAPK inhibitor). Cell proliferation was tested using the Cell Counting Kit-۸ assay. Collagen type IV and laminin were tested by ELISA. Chemerin expression was detected by qRT-PCR. The chemerin receptor was detected by immunohistochemistry. Interleukin-۶ (IL-۶), tumor necrosis factor-a (TNF-α), nuclear factor-κBp-p۶۵ (NF-κB p-p۶۵), transforming growth factor-β (TGF-β), and p-P۳۸ mitogen-activated protein kinase (p-P۳۸ MAPK) were evaluated by western blot.Results: High-glucose culture increased the expression of the chemerin receptor. α-LA inhibited HMC proliferation. Chemerin overexpression increased collagen type IV and laminin expression. P۳۸ MAPK signaling was activated by chemerin, resulting in up-regulation of IL-۶, TNF-α, NF-κB p-p۶۵, and TGF-β. SB۲۰۳۵۸۰, PDTC, and α-LA reversed the effects of chemerin, reducing IL-۶, TNF-α, NF-κB p-p۶۵, and TGF-β expression. Conclusion: Chemerin might be involved in the occurrence and development of DN. α-LA might prevent the effects of chemerin on the progression of DN, possibly via the P۳۸ MAPK pathway.

Keywords:

Alpha , lipoic acid Chemerin Diabetic nephropathy Nuclear factor , kappa , B P۳۸ mitogen , activated , protein kinases