Myeloid-derived growth factor regulates high glucose-mediated apoptosis of gingival fibroblasts and induce AKT pathway activation and nuclear factor KB pathway inhibition

Background: /purpose: Periodontal disease is a chronic inflammatory disease that occurs in the tissues that support and attach teeth. There is considerable evidence of a rela-tionship between diabetes and periodontal disease. Emerging studies have reported that myeloid-derived growth factor (MYDGF) can inhibit apoptosis and inflammation. The purpose of this study was to investigate whether MYDGF mediates the role of hyperglycemia in fibro-blasts in periodontitis tissues.Materials and methods: Fibroblasts were isolated and cultured from normal gums. Gene expression levels were detected by RT-PCR. The protein level was detected by western blot-ting. Cell viability was determined by MTT assay. To investigate the role of MYDGF, the plasmid was transfected into fibroblasts. The expression levels of cytokines were determined by ELISA.Results: High glucose can down-regulate the expression of MYDGF in human gingival fibroblasts in a time-dependent manner, and decrease the fibroblast activity. SOD level was decreased and MDA level was increased in gingival fibroblasts by high glucose. High glucose up -regulates pro-apoptotic indicator Bax, down-regulates anti-apototic indicator Bcl-2, and increased endoplasmic reticulum stress related indicators Nox 2, GRP78, ATF6, and PERK. In addition, high glucose increased TNF-a, IL-1b, IL-8 and CXCL1 protein levels in fibroblasts. Our study also found that high glucose inhibits the AKT signaling pathway and activates the nu-clear factor kB (NF-kB) pathway. Interestingly, overexpression of MYDGF reversed these ef-fects.Conclusion: MYDGF is down-regulated in gingival fibroblasts induced by high glucose. Overex-pression of MYDGF inhibits apoptosis induced by high glucose, inhibits oxidative stress and cytokine secretion of gingival fibroblasts induced by high glucose, and induces AKT pathway activation and NF-kB pathway inhibition. 2022 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).

Automated summary

The purpose of this study was to investigate the role of MYDGF in fibroblasts in periodontitis tissues induced by high glucose. The results showed that high glucose down-regulated the expression of MYDGF, leading to decreased cell viability, increased apoptosis and oxidative stress, as well as elevated expression of pro-inflammatory cytokines. However, overexpression of MYDGF reversed these effects.