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

Document Type : Original Article

Authors

Department of Endocrinology, First Affiliated Hospital of Harbin Medical University, Harbin, China

10.22038/ijbms.2021.50792.11570

Abstract

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 P38 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 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-α), nuclear factor-κBp-p65 (NF-κB p-p65), transforming growth factor-β (TGF-β), 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. α-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-α, NF-κB p-p65, and TGF-β. SB203580, PDTC, and α-LA reversed the effects of chemerin, reducing IL-6, TNF-α, NF-κB p-p65, 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 P38 MAPK pathway.

Keywords


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