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Early in acute injury, macrophages primarily rely on glycolysis and the pentose phosphate pathway, transitioning to a pro-inflammatory phenotype. Persistent activation of pro-inflammatory macrophages can lead to tissue damage. As the metabolic microenvironment evolves, the expression of glycolysis-related genes is suppressed, while the expression of genes related to oxidative phosphorylation and the tricarboxylic acid cycle is upregulated, promoting the gradual shift of macrophages toward an anti-inflammatory phenotype. This process plays a crucial role in tissue repair and remodeling. However, sustained activation of anti-inflammatory macrophages may contribute to the development of fibrosis. Therefore, metabolic reprogramming of macrophages presents a novel potential therapeutic target for intervening in inflammatory injury and stromal fibrosis. The high plasticity of macrophages is essential for tissue repair and regeneration, as they regulate inflammation, promote angiogenesis, and facilitate extracellular matrix remodeling, thereby restoring tissue homeostasis. This capability holds promise for the treatment of various conditions, including chronic wounds, fibrotic diseases, and inflammatory disorders.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1793796","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T04:23:36Z","timestamp":1783916616000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunometabolic control of macrophage plasticity in wound healing: mechanistic insights and therapeutic opportunities"],"prefix":"10.3389","volume":"17","author":[{"given":"Lijing","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Lishui Central Hospital","place":["Lishui, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyou","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Lishui Central Hospital","place":["Lishui, 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