Journal
INTERNATIONAL JOURNAL OF ORAL SCIENCE
Volume 13, Issue 1, Pages -Publisher
SPRINGERNATURE
DOI: 10.1038/s41368-021-00116-6
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Funding
- National Natural Science Foundation of China [81870779, 81991500, 81991502]
- International Cooperation Project of Chengdu Municipal Science and Technology Bureau [2015-GH02-00035-HZ]
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Hyperglycemia leads to chronic low-grade inflammation, contributing to diabetes-related tissue lesions like inflammatory bone loss in periodontitis. The study identifies the role of GLUT1 in macrophage senescence and SASP response triggered by high glucose in diabetes.
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 SASP-spreading 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 mRNA 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 mTOR 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.
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