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Macrophage\u2010fibroblast crosstalk is central to this process. Progranulin (PGRN) is involved in tissue repair, yet its intercellular transport and signaling mechanisms remain unclear. This study investigates how macrophage\u2010derived PGRN, via extracellular vesicles (EVs), regulates fibroblast behavior during healing. Using murine scRNA\u2010seq and transwell co\u2010culture, we found that macrophages suppress fibroblast activation. Mechanistically, macrophage\u2010derived PGRN was packaged into EVs and internalized by fibroblasts, upregulating DnaJ heat shock protein family member C3 (DNAJC3). Rescue experiments confirmed that DNAJC3 is essential for PGRN to inhibit the serum response factor (SRF)\/alpha\u2010smooth muscle actin (\u03b1\u2010SMA)\/connective tissue growth factor (CTGF) pathway. In a mouse wound model, PGRN\u2010enriched EVs accelerated healing and improved healing quality, while EVs from\n                    <jats:italic>Grn<\/jats:italic>\n                    \u2010silenced macrophages were less effective. We identify a novel EV\u2010mediated pathway: macrophage PGRN targets fibroblast DNAJC3 to suppress fibrotic signaling. This reveals a fundamental regulatory mechanism and highlights macrophage EVs as promising natural therapeutics for fibrotic skin disorders.\n                  <\/jats:p>","DOI":"10.1096\/fj.202602086r","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T10:26:28Z","timestamp":1787048788000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Macrophage\u2010Derived Extracellular Vesicles Deliver Progranulin to Alleviate Skin Wound Fibrosis"],"prefix":"10.1096","volume":"40","author":[{"given":"Xulong","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Forensic Medicine Xuzhou Medical University  Xuzhou Jiangsu China"},{"name":"Jiangsu Medical Engineering Research Center of Gene Detection Xuzhou Medical University  Xuzhou Jiangsu 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