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. alpha-lipoic acid (alpha-LA) is a potent antioxidant involved in the reduction of diabetic symptoms. This study aimed to investigate the relationship between chemerin and P38 MAPK in the progression of diabetic nephropathy (DN) and examine the effects of alpha-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, alpha-LA, PDTC (pyrrolidine dithiocarbamate ammonium, NF Kappa B p65 inhibitor), and/or SB203580 (P38 MAPK inhibitor). Cell proliferation was tested using the Cell Counting Kit-8 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-6 (IL-6), tumor necrosis factor-a (TNF-alpha), nuclear factor-Kappa Bp-p65 (NF-Kappa B p-p65), transforming growth factor-beta (TGF-beta), and p-P38 mitogen-activated protein kinase (p-P38 MAPK) were evaluated by western blot. Results: High-glucose culture increased the expression of the chemerin receptor. alpha-LA inhibited HMC proliferation. Chemerin overexpression increased collagen type IV and laminin expression. P38 MAPK signaling was activated by chemerin, resulting in up-regulation of IL-6, TNF-alpha, NF-Kappa B p-p65, and TGF-beta. SB203580, PDTC, and alpha-LA reversed the effects of chemerin, reducing IL-6, TNF-alpha, NF-Kappa B p-p65, and TGF-beta expression. Conclusion: Chemerin might be involved in the occurrence and development of DN. alpha-LA might prevent the effects of chemerin on the progression of DN, possibly via the P38 MAPK pathway.

Automated summary

Chemerin is associated with diabetic nephropathy (DN) progression via the P38 MAPK pathway, while alpha-lipoic acid (alpha-LA) may prevent the effects of Chemerin on DN progression through the same pathway.