{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T22:53:14Z","timestamp":1790549594789,"version":"4.1.0"},"reference-count":56,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T00:00:00Z","timestamp":1614038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017R1D1AB03029770"],"award-info":[{"award-number":["2017R1D1AB03029770"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2016K1A4A3914725"],"award-info":[{"award-number":["2016K1A4A3914725"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019H1D3A2A02102074"],"award-info":[{"award-number":["2019H1D3A2A02102074"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004470","name":"Daewoong Pharmaceutical Company","doi-asserted-by":"publisher","award":["."],"award-info":[{"award-number":["."]}],"id":[{"id":"10.13039\/501100004470","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Keloid and hypertrophic scars are skin fibrosis-associated disorders that exhibit an uncontrollable proliferation of fibroblasts and their subsequent contribution to the excessive accumulation of extracellular matrix (ECM) in the dermis. In this study, to elucidate the underlying mechanisms, we investigated the pivotal roles of epidermal growth factor (EGF) in modulating fibrotic phenotypes of keloid and hypertrophic dermal fibroblasts. Our initial findings revealed the molecular signatures of keloid dermal fibroblasts and showed the highest degree of skin fibrosis markers, ECM remodeling, anabolic collagen-cross-linking enzymes, such as lysyl oxidase (LOX) and four LOX-like family enzymes, migration ability, and cell\u2013matrix traction force, at cell\u2013matrix interfaces. Furthermore, we observed significant EGF-mediated downregulation of anabolic collagen-cross-linking enzymes, resulting in amelioration of fibrotic phenotypes and a decrease in cell motility measured according to the cell\u2013matrix traction force. These findings offer insight into the important roles of EGF-mediated cell\u2013matrix interactions at the cell\u2013matrix interface, as well as ECM remodeling. Furthermore, the results suggest their contribution to the reduction of fibrotic phenotypes in keloid dermal fibroblasts, which could lead to the development of therapeutic modalities to prevent or reduce scar tissue formation.<\/jats:p>","DOI":"10.3390\/ijms22042198","type":"journal-article","created":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T12:40:16Z","timestamp":1614084016000},"page":"2198","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Ameliorating Fibrotic Phenotypes of Keloid Dermal Fibroblasts through an Epidermal Growth Factor-Mediated Extracellular Matrix Remodeling"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7193-0278","authenticated-orcid":false,"given":"Hyunbum","family":"Kim","sequence":"first","affiliation":[{"name":"Soonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, Cheonan-si 31151, Korea"},{"name":"School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurensia Danis","family":"Anggradita","sequence":"additional","affiliation":[{"name":"Soonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, Cheonan-si 31151, Korea"},{"name":"Department of Integrated Biomedical Science, Soonchunhyang University, Asan-si 31538, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun-Jae","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon-si 14584, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Sik","family":"Hur","sequence":"additional","affiliation":[{"name":"Soonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, Cheonan-si 31151, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joonsuk","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon-si 14584, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel Suk-Yeon","family":"Hwang","sequence":"additional","affiliation":[{"name":"School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7865-5013","authenticated-orcid":false,"given":"Seung Min","family":"Nam","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon-si 14584, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5558-5171","authenticated-orcid":false,"given":"Yongsung","family":"Hwang","sequence":"additional","affiliation":[{"name":"Soonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, Cheonan-si 31151, Korea"},{"name":"Department of Integrated Biomedical Science, Soonchunhyang University, Asan-si 31538, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"328e","DOI":"10.1097\/PRS.0000000000001538","article-title":"Heat Shock Protein 90 Inhibitor Decreases Collagen Synthesis of Keloid Fibroblasts and Attenuates the Extracellular Matrix on the Keloid Spheroid Model","volume":"136","author":"Lee","year":"2015","journal-title":"Plast. 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