Journal of clinical periodontology · 2025
Exosomes Derived From Human Gingival Mesenchymal Stem Cells Induce Metabolic Reprogramming of Inflammatory Macrophages.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Wang Jialu, Hu Yingzhe, Wang Zhiguo, Fan Chun, Liu Ye, Xie Yutong, Liu Lubin, Yang Jingshu, Xu Quanchen
Аннотация
AIM: To investigate the influence and mechanism of exosomes derived from human gingival mesenchymal stem cells (GMSC-Exo) regulating macrophage polarisation through metabolic reprogramming.
MATERIALS AND METHODS: Human acute monocytic leukaemia cells (THP-1)-derived macrophages were treated with GMSC-Exo or Porphyromonas gingivalis lipopolysaccharide (P.g-LPS) in vitro. Metabolic inhibitors were used to study the role of metabolic reprogramming in GMSC-Exo-induced polarisation, while the hypoxia-inducible factor-1 alpha (HIF-1α) modulators were employed to explore the HIF-1α signalling pathway's impact on macrophage metabolic reprogramming. The impact of GMSC-Exo on periodontitis and macrophage metabolism was assessed using a rat model in vivo.
RESULTS: In vitro experiments confirmed that GMSC-Exo promoted the polarisation of macrophages from pro-inflammatory M1 type (classically activated) to anti-inflammatory M2 type (alternatively activated) by promoting metabolic reprogramming (glycolysis to oxidative phosphorylation). In this process, the activation of the HIF-1α signalling pathway was inhibited. In vivo experiments revealed that GMSC-Exo could regulate the inflammatory microenvironment of periodontal tissue and the metabolic pattern of macrophages.
CONCLUSION: By inhibiting the activation of HIF-1α signalling pathway, GMSC-Exo trigger metabolic reprogramming in macrophages, thereby regulating the macrophage transformation from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype. This change enhances the local inflammatory environment, aiding tissue repair and regeneration.
MATERIALS AND METHODS: Human acute monocytic leukaemia cells (THP-1)-derived macrophages were treated with GMSC-Exo or Porphyromonas gingivalis lipopolysaccharide (P.g-LPS) in vitro. Metabolic inhibitors were used to study the role of metabolic reprogramming in GMSC-Exo-induced polarisation, while the hypoxia-inducible factor-1 alpha (HIF-1α) modulators were employed to explore the HIF-1α signalling pathway's impact on macrophage metabolic reprogramming. The impact of GMSC-Exo on periodontitis and macrophage metabolism was assessed using a rat model in vivo.
RESULTS: In vitro experiments confirmed that GMSC-Exo promoted the polarisation of macrophages from pro-inflammatory M1 type (classically activated) to anti-inflammatory M2 type (alternatively activated) by promoting metabolic reprogramming (glycolysis to oxidative phosphorylation). In this process, the activation of the HIF-1α signalling pathway was inhibited. In vivo experiments revealed that GMSC-Exo could regulate the inflammatory microenvironment of periodontal tissue and the metabolic pattern of macrophages.
CONCLUSION: By inhibiting the activation of HIF-1α signalling pathway, GMSC-Exo trigger metabolic reprogramming in macrophages, thereby regulating the macrophage transformation from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype. This change enhances the local inflammatory environment, aiding tissue repair and regeneration.