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The mechanism is closely related to TGF\u2010\u03b21 pathways. However, the reported effects of applying ACEIs during scar formation are unclear. Hence, we explored the anti\u2010fibrotic effects of an ACEI and the molecular mechanisms involved in a mouse scar model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>After a full\u2010thickness skin wound operation, ACE wild\u2010type mice were randomly assigned to receive either ramipril, losartan or hydralazine p.o. ACE knockout (KO) mice and negative control mice only received vehicle (water). Wound\/scar widths during wound healing and histological examinations were recorded at the final day. The ability of ACEI to reduce fibrosis <jats:italic>via<\/jats:italic> TGF\u2010\u03b21 signalling was evaluated <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>ACE KO mice and mice that received ramipril showed narrower wound\/scar width, reduced fibroblast proliferation, decreased collagen and TGF\u2010\u03b21 expression. ACEI attenuated the phosphorylation of small mothers against decapentaplegic (Smad2\/3) and TGF\u2010\u03b2\u2010activated kinase 1 (TAK1) both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. The expression of ACE\u2010related peptides varied in murine models with different drug treatments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>ACEI showed anti\u2010fibrotic properties in scar formation by mediating downstream peptides to suppress TGF\u2010\u03b21\/Smad and TGF\u2010\u03b21\/TAK1 pathways. These findings suggest that dual inhibition of Smad and TAK1 signalling by ACEI is a useful strategy for the development of new anti\u2010fibrotic agents.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14489","type":"journal-article","created":{"date-parts":[[2018,8,30]],"date-time":"2018-08-30T05:03:04Z","timestamp":1535605384000},"page":"4239-4252","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Angiotensin\u2010converting enzyme inhibitor works as a scar formation inhibitor by down\u2010regulating Smad and TGF\u2010\u03b2\u2010activated kinase 1 (TAK1) pathways in mice"],"prefix":"10.1111","volume":"175","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4951-0960","authenticated-orcid":false,"given":"Wei\u2010Qiang","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Plastic Surgery, Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou Zhejiang Province 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