首页|TREM2-mediated Macrophage Glycolysis Promotes Skin Wound Angiogenesis via the Akt/mTOR/HIF-1α Signaling Axis
TREM2-mediated Macrophage Glycolysis Promotes Skin Wound Angiogenesis via the Akt/mTOR/HIF-1α Signaling Axis
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Objective:The trigger receptor expressed on myeloid cells-2(TREM2)pathway in myeloid cells is a key disease-inducing immune signaling hub that is essential for detecting tissue damage and limiting its pathological spread.However,the role and potential mechanisms of TREM2 in wound repair remain unclear.The purpose of this study was to determine the role and mechanism of TREM2 in skin wound healing in mice.Methods:Immunofluorescence staining was used to determine the expression and cellular localization of TREM2 and test the effects of TREM2 knockout on angiogenesis,glycolysis,and lactylation in skin tissue.Western blotting was used to analyze the expression of the Akt/mTOR/HIF-1α signaling pathway in the wounded skin tissues of wild-type(WT)and TREM2 knockout mice.A coimmunoprecipitation assay was used to determine whether HIF-1α,which mediates angiogenesis,is modified by lactylation.Results:The number of TREM2+macrophages was increased,and TREM2+macrophages mediated angiogenesis after skin injury.TREM2 promoted glycolysis and lactylation in macrophages during wound healing.Mechanistically,TREM2 promoted macrophage glycolysis and angiogenesis in wounded skin tissues by activating the Akt/mTOR/HIF-lα signaling pathway.HIF-1α colocalized with Klac to mediate lactylation in macrophages,and lactate could stabilize the expression of the HIF-1α protein through lactylation.Lactate treatment ameliorated the impaired angiogenesis and delayed wound healing in wounded skin in TREM2 knockout mice.Conclusion:TREM2+macrophage-mediated glycolysis can promote angiogenesis and wound healing.Our findings provide an effective strategy and target for promoting skin wound healing.
Department of Dermatology,Traditional Chinese and Western Medicine Hospital of Wuhan,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China
Hubei Provincial Key Laboratory of Skin Infection and Immunity,Wuhan No.1 Hospital,Wuhan 430022,China
Department of Dermatology,Institute of Dermatology,Chinese Academy of Medical Sciences and Peking Union Medical College,Nanjing 210000,China
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