ENTR1 regulates periodontitis by modulating macrophage M1 polarization via AMPK activation

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2025-03-05 DOI:10.1016/j.lfs.2025.123525

Xi Wang , Houda Gui , Chenghang Liu , Fenglei Huo , Weipeng Lan , Xingyan Zhu , Wenhao Wang , Anquan Ma , Jing Lan

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引用次数: 0

Abstract

Aims

Periodontitis is a chronic inflammatory disorder arising from an imbalance between oral microbiota and the host's immune response, with macrophages as pivotal targets for prevention and treatment. Endosome-associated Trafficking Regulator 1 (ENTR1) is indispensable for protein trafficking and implant osseointegration. However, its specific role in periodontitis has yet to be clarified. This research seeks to explore the effects of ENTR1 on macrophage polarization, elucidate its mechanisms, and evaluate its regulatory functions in the regeneration of periodontal tissues.

Materials and methods

A ligature-induced periodontitis mouse model was established to investigate the correlation between macrophage polarization markers and ENTR1 expression. Techniques including qRT-PCR, Western blot, ELISA, flow cytometry, and immunofluorescence staining were utilized to evaluate the impact of ENTR1 on macrophage polarization under inflammatory stimuli. Micro-CT and histological staining were applied to assess periodontal bone resorption. The interaction between ENTR1 and AMP-activated protein kinase (AMPK) was explored through Western blot and co-immunoprecipitation, further validated by applying the AMPK inhibitor Compound C (CpC).

Key findings

ENTR1 expression was down-regulated in the mice with periodontitis relative to healthy controls. Overexpressing ENTR1 suppressed macrophage M1 polarization and mitigated bone loss in periodontitis, while knocking down ENTR1 exacerbated these effects. ENTR1 directly interacted with AMPK, enhancing its phosphorylation. Furthermore, the inhibitory impact of ENTR1 on macrophage M1 polarization and inflammation-induced alveolar bone resorption were partially attenuated by CpC treatment.

Significance

ENTR1 regulates periodontitis by suppressing macrophage M1 polarization through enhancing AMPK phosphorylation, presenting a promising therapeutic target for its prevention and management.

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.