Metformin ameliorates HMGB1-mediated oxidative stress through mTOR pathway in experimental periodontitis

作者全名："Sun, Boyang; Ying, Siqi; Ma, Qian; Li, Han; Li, Jie; Song, Jinlin"

作者地址："[Sun, Boyang; Ying, Siqi; Ma, Qian; Li, Han; Li, Jie; Song, Jinlin] Chongqing Med Univ, Coll Stomatol, Chongqing 400016, Peoples R China; [Sun, Boyang; Ying, Siqi; Ma, Qian; Li, Han; Li, Jie; Song, Jinlin] Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing 400016, Peoples R China; [Sun, Boyang; Ying, Siqi; Ma, Qian; Li, Han; Li, Jie; Song, Jinlin] Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing 400016, Peoples R China; [Sun, Boyang; Ying, Siqi; Ma, Qian; Li, Han; Li, Jie; Song, Jinlin] Chongqing Med Univ, Coll Stomatol, 426 Songshibei Road, Chongqing 401147, Peoples R China"

通信作者："Sun, BY; Ying, SQ; Ma, Q; Li, H; Li, J; Song, JL (通讯作者)，Chongqing Med Univ, Coll Stomatol, 426 Songshibei Road, Chongqing 401147, Peoples R China."

来源：GENES & DISEASES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000995862700001

JCR分区：Q1

影响因子：6.9

年份：2023

卷号：10

期号：2

开始页：542

结束页：553

文献类型：Article

关键词：Autophagy; Metformin; Oxidative stress; Periodontal ligament cells; Periodontitis

摘要："Periodontitis is an oral chronic inflammatory disease. Inhibiting tissue destruction and promoting tissue regeneration are important means for the treatment of periodontitis. Metformin not only has hypoglycemic effect but also has anti-inflammatory effect. Metformin has been shown to inhibit oxidative stress and activate autophagy through AMPK/mTOR pathway. High mobility group box 1 (HMGB1) has been implicated in the pathogenesis of many inflammatory diseases including periodontitis, it can participate in the induction of oxidative stress. HMGB1 is an autophagy regulator under oxidative stress, which can activate mTOR pathway. However, it is not clear whether metformin is related to HMGB1 and its mechanism in the process of periodontitis. Cell viability and expression of inflammatory cytokines were clarified by Cell Counting Kit-8, real-time PCR and enzyme-linked immunosorbent assay. Western blot and immunofluorescence were conducted to determine HMGB1 intracellular localization and expression of autophagy-associated proteins in vitro. Experimental periodontitis mice model was induced by administering a ligature. Immunohistochemistry was performed to detect the expression and localization of HMGB1 in vivo. The results of CCK-8, real-time PCR, enzyme-linked immunosorbent assay, Western blot and immunofluorescence showed lipopolysaccharide (LPS) treatment inhibited cell viability, and increased HMGB1 expression at a dose-independent manner. Metformin can reduce the effect of LPS. It also improves autophagy pathway inhibited by LPS and down-regulates mTOR expression. In addition, metformin attenuated alveolar bone resorption induced by ligation. This study provides new evidence for that metformin is a potential drug for the treatment of periodontitis and HMGB1 may be a potential target for periodontal intervention. 2021 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/)."

基金机构："National Natural Science Foundation of China [81771082, 31971282]; Scientific and Technological Research Program of Chongqing Municipal Education Commission, China [KJQN202000417]; Chongqing Graduate Tutor Team, China"

基金资助正文："This work was supported by the National Natural Science Foundation of China (No. 81771082, 31971282), Scientific and Technological Research Program of Chongqing Municipal Education Commission, China (No. KJQN202000417) and Chongqing Graduate Tutor Team, China (2019)."