{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:50:27Z","timestamp":1787323827069,"version":"build-2736575974"},"reference-count":42,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2024JJ5130"],"award-info":[{"award-number":["2024JJ5130"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hypertrophic scar is a pathological consequence of abnormal wound healing, marked by excessive fibroblast proliferation and extracellular matrix (ECM) accumulation. Macrophage\u2010to\u2010myofibroblast transformation (MMT) plays a key role in this process, but its regulatory mechanisms remain under investigation. This study found that microfibril\u2010associated protein 4 (MFAP4) is significantly upregulated in mice scar tissue and is closely associated with the MMT process. In a mouse excision injury model, knockdown of MFAP4 in\u00a0vivo macrophages using adeno\u2010associated virus (AAV)\u2010mediated RNA interference significantly reduced dermal thickening and disorganized collagen fibre deposition in mice scar tissues. Macrophage infiltration, expression of the myofibroblast marker \u03b1\u2010SMA, and the proportion of MMT cells (F4\/80\n                    <jats:sup>+<\/jats:sup>\n                    \u03b1\u2010SMA\n                    <jats:sup>+<\/jats:sup>\n                    ) were shown to be remarkably reduced. In\u00a0vitro, TGF\u2010\u03b21 induces elevated MFAP4 expression within mouse\u2010derived bone marrow\u2010derived macrophages (BMDMs) and promotes MMT. MFAP4 knockdown inhibits TGF\u2010\u03b21\u2010induced myofibroblast transformation and expression of ECM synthesis\u2010related molecules (\u03b1\u2010SMA, Col\u2010I and Vimentin), while MFAP4 overexpression enhances these effects. Mechanistic studies suggest that MFAP4 regulates this process via the TGF\u2010\u03b2\/Smad3 signalling activation. MFAP4 promotes Smad3 phosphorylation (p\u2010Smad3), and overexpression of Smad3 in MFAP4\u2010knockdown mouse\u2010derived BMDMs reverses the inhibitory effects of MFAP4 deficiency on MMT and ECM synthesis. These results reveal a key role for the MFAP4\u2010TGF\u2010\u03b2\/Smad3 axis in regulating MMT\u2010driven scar formation, providing novel insights into the mechanisms of hypertrophic scarring in mice and underlying therapeutic targets for clinical intervention.\n                  <\/jats:p>","DOI":"10.1111\/exd.70314","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T08:05:11Z","timestamp":1783670711000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>MFAP4<\/scp>\n                    Promotes Scar Formation by Regulating Macrophage\u2010Myofibroblast Transformation Through Activation of the\n                    <scp>TGF<\/scp>\n                    \u2010\u03b2\/Smad3 Signalling Pathway"],"prefix":"10.1111","volume":"35","author":[{"given":"Zhu","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Medical Aesthetics Hunan Aerospace Hospital  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Dermatology The Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinglin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology The Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology The Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Aesthetics Hunan Aerospace 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