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The cell counting kit\u20108 assay and quantitative reverse transcription polymerase chain reactions were performed to screen the functional peptides contained within ADSC\u2010CM. RNA\u2010seq, western blot, a back skin excisional model of BALB\/c mice, the peptide pull\u2010down assay, rescue experiments, untargeted metabolomics, and mixOmics analysis were performed to thoroughly understand the functional mechanism of selected peptide.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 93, 827, 1108, and 631 peptides were identified in ADSC\u2010CM at 0, 24, 48, and 72\u2009h of conditioning, respectively. A peptide named ADSCP2 (DENREKVNDQAKL) derived from ADSC\u2010CM inhibited collagen and ACTA2 mRNAs in hypertrophic scar fibroblasts. Moreover, ADSCP2 facilitated wound healing and attenuated collagen deposition in a mouse model. ADSCP2 bound with the pyruvate carboxylase (PC) protein and inhibited PC protein expression. Overexpressing PC rescued the reduction in collagen and ACTA2 mRNAs caused by ADSCP2. Untargeted metabolomics identified 258 and 447 differential metabolites in the negative and positive mode, respectively, in the ADSCP2\u2010treated group. The mixOmics analysis, which integrated RNA\u2010seq and untargeted metabolomics data, provided a more holistic view of the functions of ADSCP2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Overall, a novel peptide derived from ADSC\u2010CM, named ADSCP2, attenuated hypertrophic scar fibrosis in vitro and in vivo, and the novel peptide ADSCP2 might be a promising drug candidate for clinical scar therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.14010","type":"journal-article","created":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T10:35:07Z","timestamp":1687862107000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The adipose\u2010derived stem cell peptide ADSCP2 alleviates hypertrophic scar fibrosis via binding with pyruvate carboxylase and remodeling the metabolic 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