Intermittent hyperglycaemia induces macrophage dysfunction by extracellular regulated protein kinase‐dependent PKM2 translocation in periodontitis

Author:

Sun Yuezhang1,Cui Aimin1,Dong Hao1,Nie Lulingxiao1,Yue Ziqi1,Chen Jiao1,Leung Wai Keung2,Wang Jian1,Wang Qi13ORCID

Affiliation:

1. State Key Laboratory of Orval Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology Sichuan University Chengdu China

2. Periodontology and Implant Dentistry Division, Faculty of Dentistry The University of Hong Kong Hong Kong China

3. Sichuan Provincial Engineering Research Center of Oral Biomaterials, Sichuan University Chengdu China

Abstract

AbstractEarly fluctuations in blood glucose levels increased susceptibility to macrophage dysfunction. However, the underlying pathological mechanisms linking glucose variations and macrophage dysregulation remains elusive. In current study, we established an animal model of transient intermittent hyperglycaemia (TIH) to simulate early fluctuations in blood glucose levels. Our findings revealed that both TIH and diabetic group exhibited more severe periodontal lesions and increased secretion of pro‐inflammatory cytokines compared to healthy controls. In immortalized bone marrow–derived macrophages (iBMDMs), phagocytosis and chemotaxis were impaired with transient and lasting hyperglycaemia, accompanied by enhanced glycolysis. We also found that TIH activated pyruvate kinase M2 (PKM2) through the phosphorylation of extracellular regulated protein kinase (ERK) in vivo, particularly at dimeric levels. In macrophage cultured with TIH, PKM2 translocated into the nucleus and involved in the regulating inflammatory genes, including TNF‐α, IL‐6 and IL‐1β. PKM2 translocation and secretion of inflammatory cytokines were attenuated by PD98059, while PKM2 tetramer activator TEPP‐46 prevented the formation of dimeric PKM2 in macrophages. Moreover, inhibition of glycolysis alleviated the TIH‐induced pro‐inflammatory cytokines. In conclusion, our manuscript provides a rationale for understanding how TIH modulates metabolic rewiring and dysfunction in macrophages via ERK‐dependent PKM2 nuclear translocation.

Funder

Chengdu Municipal Science and Technology Program

Science and Technology Department of Sichuan Province

National Natural Science Foundation of China

Publisher

Wiley

Reference39 articles.

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3