Alpha-lipoic Acid Could Attenuate the Effect of Chemerin-induced Diabetic Nephropathy Progression

Overview

Journal Iran J Basic Med Sci

Publisher Mashhad University of Medical Sciences

Specialty General Medicine

Date 2021 Nov 22

PMID 34804428

Citations 4

Authors

Hong Zhang

Jiawei Mu

Jinqiu Du

Ying Feng

Wenhui Xu

Mengmeng Bai

Huijuan Zhang

Affiliations

Soon will be listed here.

Abstract

Objectives: 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.

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References

Yi X, Xu L, Hiller S, Kim H, Nickeleit V, James L . Reduced expression of lipoic acid synthase accelerates diabetic nephropathy. J Am Soc Nephrol. 2011; 23(1):103-11. PMC: 3269922. DOI: 10.1681/ASN.2011010003. View

Hu W, Feng P . Elevated serum chemerin concentrations are associated with renal dysfunction in type 2 diabetic patients. Diabetes Res Clin Pract. 2010; 91(2):159-63. DOI: 10.1016/j.diabres.2010.11.016. View

Chukanova E, Chukanova A . [Alpha-lipoic acid in the treatment of diabetic polyneuropathy]. Zh Nevrol Psikhiatr Im S S Korsakova. 2018; 118(1):103-109. DOI: 10.17116/jnevro201811811103-109. View

Sadeghiyan Galeshkalami N, Abdollahi M, Najafi R, Baeeri M, Jamshidzade A, Falak R . Alpha-lipoic acid and coenzyme Q10 combination ameliorates experimental diabetic neuropathy by modulating oxidative stress and apoptosis. Life Sci. 2018; 216:101-110. DOI: 10.1016/j.lfs.2018.10.055. View

Saleh H, El-Sayed Y, Naser S, Eltahawy A, Onoda A, Umezawa M . Efficacy of α-lipoic acid against cadmium toxicity on metal ion and oxidative imbalance, and expression of metallothionein and antioxidant genes in rabbit brain. Environ Sci Pollut Res Int. 2017; 24(31):24593-24601. DOI: 10.1007/s11356-017-0158-0. View

Papanas N, Ziegler D . Efficacy of α-lipoic acid in diabetic neuropathy. Expert Opin Pharmacother. 2014; 15(18):2721-31. DOI: 10.1517/14656566.2014.972935. View

Kim J, Bhattacharjee R, Dayyat E, Snow A, Kheirandish-Gozal L, Goldman J . Increased cellular proliferation and inflammatory cytokines in tonsils derived from children with obstructive sleep apnea. Pediatr Res. 2009; 66(4):423-8. PMC: 2892472. DOI: 10.1203/PDR.0b013e3181b453e3. View

Salehi B, Yilmaz Y, Antika G, Tumer T, Mahomoodally M, Lobine D . Insights on the Use of α-Lipoic Acid for Therapeutic Purposes. Biomolecules. 2019; 9(8). PMC: 6723188. DOI: 10.3390/biom9080356. View

Chamberlain J, Rhinehart A, Shaefer Jr C, Neuman A . Diagnosis and Management of Diabetes: Synopsis of the 2016 American Diabetes Association Standards of Medical Care in Diabetes. Ann Intern Med. 2016; 164(8):542-52. DOI: 10.7326/M15-3016. View

10.

Snyder M, Gibbs L, Lindsay T . Treating Painful Diabetic Peripheral Neuropathy: An Update. Am Fam Physician. 2016; 94(3):227-34. View

11.

Yeh C, Sturgis L, Haidacher J, Zhang X, Sherwood S, Bjercke R . Requirement for p38 and p44/p42 mitogen-activated protein kinases in RAGE-mediated nuclear factor-kappaB transcriptional activation and cytokine secretion. Diabetes. 2001; 50(6):1495-504. DOI: 10.2337/diabetes.50.6.1495. View

12.

. Standards of Medical Care in Diabetes-2016 Abridged for Primary Care Providers. Clin Diabetes. 2016; 34(1):3-21. PMC: 4714725. DOI: 10.2337/diaclin.34.1.3. View

13.

Wang Y, Liu L, Peng W, Liu H, Liang L, Zhang X . Ski-related novel protein suppresses the development of diabetic nephropathy by modulating transforming growth factor-β signaling and microRNA-21 expression. J Cell Physiol. 2019; 234(10):17925-17936. DOI: 10.1002/jcp.28425. View

14.

Pang Y, Zhu H, Xu J, Yang L, Liu L, Li J . β-arrestin-2 is involved in irisin induced glucose metabolism in type 2 diabetes via p38 MAPK signaling. Exp Cell Res. 2017; 360(2):199-204. DOI: 10.1016/j.yexcr.2017.09.006. View

15.

Ding H, Xu Y, Jiang N . Upregulation of miR-101a Suppresses Chronic Renal Fibrosis by Regulating KDM3A via Blockade of the YAP-TGF-β-Smad Signaling Pathway. Mol Ther Nucleic Acids. 2020; 19:1276-1289. PMC: 7033461. DOI: 10.1016/j.omtn.2020.01.002. View

16.

Shang J, Wang L, Zhang Y, Zhang S, Ning L, Zhao J . Chemerin/ChemR23 axis promotes inflammation of glomerular endothelial cells in diabetic nephropathy. J Cell Mol Med. 2019; 23(5):3417-3428. PMC: 6484295. DOI: 10.1111/jcmm.14237. View

17.

Yi X, Nickeleit V, James L, Maeda N . α-Lipoic acid protects diabetic apolipoprotein E-deficient mice from nephropathy. J Diabetes Complications. 2010; 25(3):193-201. PMC: 3010318. DOI: 10.1016/j.jdiacomp.2010.07.004. View

18.

Rochette L, Ghibu S, Muresan A, Vergely C . Alpha-lipoic acid: molecular mechanisms and therapeutic potential in diabetes. Can J Physiol Pharmacol. 2015; 93(12):1021-7. DOI: 10.1139/cjpp-2014-0353. View

19.

Salama F, Anass Q, Abdelrahman A, Saeed E . Chemerin: A biomarker for cardiovascular disease in diabetic chronic kidney disease patients. Saudi J Kidney Dis Transpl. 2016; 27(5):977-984. DOI: 10.4103/1319-2442.190867. View

20.

Cakici N, Fakkel T, van Neck J, Verhagen A, Coert J . Systematic review of treatments for diabetic peripheral neuropathy. Diabet Med. 2016; 33(11):1466-1476. DOI: 10.1111/dme.13083. View