Hyperglycemia-induced Inflamm-aging Accelerates Gingival Senescence Via NLRC4 Phosphorylation

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2019 Nov 3

PMID 31676687

Citations 26

Authors

Peng Zhang

Qian Wang

Lulingxiao Nie

Rui Zhu

Xinyi Zhou

Pengfei Zhao

Ning Ji

Xing Liang

Yi Ding

Quan Yuan

Qi Wang

Affiliations

Soon will be listed here.

Abstract

Inflamm-aging was recently affiliated with the progression of diabetic complications. Local cellular senescence together with senescence-associated secretory phenotype (SASP) are the main contributors to inflamm-aging. However, little is known about their involvement in diabetic periodontitis. Gingiva is the first line of host defense in the periodontium, and macrophages are key SASP-carrying cells. Here, we explored the molecular mechanism by which hyperglycemia drives the inflamm-aging in the gingival tissue of diabetic mice and macrophages. We demonstrated that hyperglycemia increased the infiltrated macrophage senescence in gingival tissue of diabetic mice. Simultaneously, hyperglycemia elevated the local burden of senescent cells in gingival tissue and induced the serum secretion of SASP factors Moreover, , high glucose induced macrophage senescence and SASP factors secretion through phosphorylation of NLRC4, which further stimulated the NF-κB/Caspase-1 cascade via an IRF8-dependent pathway. Deletion of NLRC4 or IRF8 abolished hyperglycemia-induced cellular senescence and SASP in macrophages. In addition, we found that treatment with metformin inhibited NLRC4 phosphorylation and remarkably decreased cellular senescence and SASP in the context of hyperglycemia. Our data demonstrated that hyperglycemia induces the development of inflamm-aging in gingival tissue and suggested that NLRC4 is a potential target for treatment of diabetes-associated complications.

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