{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T22:29:01Z","timestamp":1778797741285,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,8,21]],"date-time":"2018-08-21T00:00:00Z","timestamp":1534809600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2018,8,21]],"date-time":"2018-08-21T00:00:00Z","timestamp":1534809600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:p>Transforming growth factor \u03b2 (TGF\u2010\u03b2) is a growth factor presenting important functions during tissue remodeling and hypertrophic scar (HS) formation. However, the underlying molecular mechanisms are largely unknown. In this study, we identified thrombospondin\u20104 (TSP\u20104) as a TGF\u2010\u03b21 target that essentially mediates TGF\u2010\u03b21\u2010induced scar formation both in vitro and in vivo.\u00a0The expression of TSP\u20104 was compared on both mRNA and protein levels between hypertrophic scar fibroblasts (HSFs) and normal skin fibroblast (NFs) in response to TGF\u2010\u03b21 treatment. Two signaling molecules, Smad3 and p38, were assessed for their importance in regulating TGF\u2010\u03b21\u2010mediated TSP\u20104 expression. The significance of TSP\u20104 in controlling TGF\u2010\u03b21\u2010induced proliferation, invasion, migration, and fibrosis in HSFs was analyzed by knocking down endogenous TSP\u20104 using small hairpin RNA (shRNA) (TSP\u20104 shRNA). Finally, a skin HS model was established in rats and the scar formation was compared between rats treated with vehicle (saline), TGF\u2010\u03b21, and TGF\u2010\u03b21\u2009+\u2009TSP\u20104 shRNA. The TSP\u20104 level was significantly higher in HSFs than in NFs and TGF\u2010\u03b21 more potently boosted TSP\u20104 expression in the former than in the latter. Both Smad3 and p38 essentially mediated TGF\u2010\u03b21\u2010induced TSP\u20104 expression. TSP\u20104 shRNA significantly suppressed TGF\u2010\u03b21\u2010stimulated proliferation, invasion, migration, or fibrosis of HSFs in vitro and drastically improved wound healing in vivo.\u00a0TGF\u2010\u03b21, by activating both Smad3 and p38, induces TSP\u20104, which in turn not only presents a positive feedback regulation on the activation of Smad3 and p38, but also essentially mediates TGF\u2010\u03b21\u2010induced HS formation. Targeting TSP\u20104 thus may benefit HS treatment.<\/jats:p>","DOI":"10.1002\/jcp.26877","type":"journal-article","created":{"date-parts":[[2018,8,22]],"date-time":"2018-08-22T12:15:53Z","timestamp":1534940153000},"page":"731-739","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Thrombospondin\u20104 critically controls transforming growth factor \u03b21 induced hypertrophic scar formation"],"prefix":"10.1002","volume":"234","author":[{"given":"Wei","family":"Qian","sequence":"first","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery Beijing Chao\u2010Yang Hospital, Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery Beijing Chao\u2010Yang Hospital, Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery Beijing Chao\u2010Yang Hospital, Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6911-7141","authenticated-orcid":false,"given":"Jufeng","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery Beijing Chao\u2010Yang Hospital, Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,8,21]]},"reference":[{"key":"e_1_2_5_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2005.03.022"},{"key":"e_1_2_5_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0928-0987(01)00139-7"},{"key":"e_1_2_5_1_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-2180"},{"key":"e_1_2_5_1_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.prs.0000182343.99694.28"},{"key":"e_1_2_5_1_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10983"},{"key":"e_1_2_5_1_7_1","first-page":"301","article-title":"Fibroblasts and myofibroblasts in wound healing","volume":"7","author":"Darby I. 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