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However, no available drugs can be utilized to effectively treat these scars. The transforming growth factor \u03b2 (<jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u03b2) signalling pathway regulates collagen synthesis and plays an important role in scar formation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To evaluate the anti\u2010scar effects of <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u03b2 inhibitors <jats:italic>in\u00a0vitro<\/jats:italic> and <jats:italic>in\u00a0vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Col1\u03b12\u2010luciferase reporter assay was used to screen the compounds suppress type I collagen gene transcription. Sulforhodamine B colorimetric assay and colony formation assay were used to test the compound's effect on cell proliferation. Wound healing and transwell assay were performed to test the cell migration and invasion. Western blotting, immunofluorescence, immunohistochemistry and Q\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> assay were used to determine the protein and <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> levels. 3D cell contraction assay was used to examine the cell contraction. Flow cytometry was performed to analyse cell apoptosis. Masson stain, H&amp;E stain and immunochemistry were used to analyse the scar formation <jats:italic>in\u00a0vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">WG<\/jats:styled-content>449E, as one of the most potent inhibitors, was identified to significantly downregulate the <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and protein levels of collagen in hypertrophic scar\u2010derived fibroblasts through inhibiting Smad2\/3 phosphorylation. <jats:styled-content style=\"fixed-case\">WG<\/jats:styled-content>449E inhibited the proliferation, migration and contraction of fibroblasts <jats:italic>in\u00a0vitro<\/jats:italic> and <jats:italic>in\u00a0vivo<\/jats:italic>. In addition, <jats:styled-content style=\"fixed-case\">WG<\/jats:styled-content>449E induced cell apoptosis through the activation of cleaved\u2010caspase3. Moreover, <jats:styled-content style=\"fixed-case\">WG<\/jats:styled-content>449E significantly attenuated hypertrophic scar formation and collagen deposition in a mechanical load\u2010induced mouse model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">WG<\/jats:styled-content>449E is a potential candidate for the treatment of hypertrophic scars.<jats:styled-content style=\"fixed-case\">WG<\/jats:styled-content>449E downregulates the <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and protein levels of collagen in hypertrophic scar\u2010derived fibroblasts through inhibiting Smad2\/3 phosphorylation and nucleic localization. <jats:styled-content style=\"fixed-case\">WG<\/jats:styled-content>449E blocks <jats:styled-content style=\"fixed-case\">HSF<\/jats:styled-content> migration and invasion by regulating F\u2010actin assignment. In addition, <jats:styled-content style=\"fixed-case\">WG<\/jats:styled-content>449E induces <jats:styled-content style=\"fixed-case\">HSF<\/jats:styled-content> apoptosis through the activation of cleaved\u2010caspase3.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.16028","type":"journal-article","created":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T08:04:26Z","timestamp":1571990666000},"page":"608-618","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Research on function and mechanisms of a novel small molecule <scp>WG<\/scp>449E for hypertrophic scar"],"prefix":"10.1111","volume":"34","author":[{"given":"T.","family":"Shao","sequence":"first","affiliation":[{"name":"East China Normal University and Shanghai Fengxian District Central Hospital Joint Center for Translational Medicine Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal 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