Abstract
To demonstrate glutamine (Gln) promotes acute wound healing by mediating Gln metabolism and macrophage M2 polarization through the Mitogen-Activated Protein Kinase Kinase (MEK)/Extracellular Regulated Protein Kinases (ERK)/Solute Carrier Family 1 Member 5 (SLC1A5) signaling axis.Thirty C57BL/6J mice were used to establish a full-thickness skin defect model and randomly divided into six groups (n = 5 per group): Control group, Model group, Gln treatment group (Gln), Gln combined with MEK inhibitor U0126 group (Gln + MEK inhibitor), Gln combined with GLS1 inhibitor group (Gln+GLS1 inhibitor), and Gln combined with SLC1A5 inhibitor group (Gln+SLC1A5 inhibitor). Immunofluorescence (IF) was used to detect the angiogenesis marker CD31, the fibroblast activation marker α-smooth muscle actin (α-SMA), and macrophage polarization markers (CD86 for M1, CD206 for M2). Gln upregulates the expression of SLC1A5 by activating MEK/ERK pathway, thus promoting Gln metabolic reprogramming and accelerating acute wound healing. This subsequently drives M2 macrophage polarization, angiogenesis, and tissue remodeling. Our findings elucidate the critical role of the Gln metabolism-immune regulation axis in wound repair and provide a novel therapeutic target for metabolically targeted wound interventions.
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Funding
This work was supported by the Basic Research Project of Department of Science and Technology of Yunnan Province (202201AY070001-288), Xingdian Talent Support Program medical and Health Talents Special Project, Yunnan Prvincial Clinical Orthopaedic Trauma Medical Center, and National Key Research and Development Program (2022YFC2405704).
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Yan Shi: Data curation, methodology, formal analysis, visualization, and writing - original draft. Mingheng Pan: Conceptualiza, supervision, and writing - review & editing. Xue Chen and Ye Bi: Formal analysis, and software. Xiaolong Wei and Feiyang Zheng: Investigation, formal analysis, and validation. Hao Xia: Data curation, and methodology. Xiaoqing HE: Conceptualization, funding acquisition, project administration, and writing - review & editing.
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Shi, Y., Pan, M., Chen, X. et al. Glutamine promotes acute wound healing by mediating glutamine metabolism and M2 macrophage polarization via the MEK/ERK/SLC1A5 signaling pathway. Sci Rep (2026). https://doi.org/10.1038/s41598-026-41545-9
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DOI: https://doi.org/10.1038/s41598-026-41545-9
