Diabetes fuels periodontal lesions via GLUT1-driven macrophage inflammaging  

作　　者：Qian Wang Lulingxiao Nie Pengfei Zhao Xinyi Zhou Yi Ding Qianming Chen Qi Wang 

机构地区：[1]State Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&West China Hospital of Stomatology,Sichuan University,Chengdu,China [2]Department of Prosthodontics,West China Hospital of Stomatology,Sichuan University,Chengdu,China [3]Department of Periodontology,West China Hospital of Stomatology,Sichuan University,Chengdu,China

出　　处：《International Journal of Oral Science》2021年第3期251-260,共10页国际口腔科学杂志（英文版）

基　　金：supported by the National Natural Science Foundation of China[Grant Numbers 81870779;81991500;81991502];the International Cooperation Project of Chengdu Municipal Science and Technology Bureau[Grant Number 2015-GH0200035-HZ]。

摘　　要：Hyperglycemia induces chronic low-grade inflammation(inflammaging),which is a newly identified contributor to diabetes-related tissue lesions,including the inflammatory bone loss in periodontitis.It is also a secondary senescent pattern mediated by an increased burden of senescent cells and senescence-associated secretory phenotype(SASP).Macrophage is a key SASPspreading cell and may contribute to the maintenance of SASP response in the periodontal microenvironment.Using a transgenic diabetic model(BLKS/J-Lepr^(db)/lepr^(db)mice)we identified striking senescence of the periodontium in young(18-wk)-diabetic mice accompanied by amassed p16^(+)-macrophages and enhanced early SASP response.Exposed to high glucose in vitro,bone marrow-derived macrophage(BMDM)revealed a strong GLUT1 m RNA response driving the elevated-glucose uptake.GLUT1 is a representative and facilitative glucose transporter in macrophages with potential roles in hyperglycemia-induced inflammation.In this study,both GLUT1 and the downstream GTPase Rheb expression upregulated in the gingiva of diabetic mice with impaired condition.Furthermore,SASP release and p16/p21 signaling were proven to be triggered by m TOR phosphorylation in BMDM and antagonized by restricting glucose uptake in GLUT1^(-/-)BMDM.Taken together,our findings suggest that elevated-GLUT1 sensor responded to high glucose is important for macrophage senescence and SASP response,generated as a result of hyperglycemia,and it is a potential molecular mechanism for the exacerbation of periodontitis in diabetes.

关 键 词：ELEVATED MACROPHAGE LESIONS 

分 类 号：R587.2[医药卫生—内分泌] R781.42[医药卫生—内科学]