{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:56:44Z","timestamp":1791291404083,"version":"4.3.0"},"reference-count":29,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":35,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81760558"],"award-info":[{"award-number":["81760558"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Wound Repair Regeneration"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Hypertrophic scar (HS) is characterised by excessive fibroblast proliferation and abnormal differentiation; however, the underlying molecular mechanisms remain incompletely understood. Here, we identify the collagen receptor discoidin domain receptor 1 (DDR1) as a key regulator of fibroblast activation during HS formation. We observed markedly increased expression and phosphorylation of DDR1 in human HS tissues compared with adjacent normal skin. To investigate the functional role of DDR1, primary fibroblasts derived from human HS tissues were stimulated with collagen III to induce DDR1 activation in\u00a0vitro. DDR1 activation significantly enhanced fibroblast proliferation and promoted myofibroblast differentiation, as evidenced by increased collagen III and \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA) expression. Concomitantly, DDR1 activation suppressed the expression of the tumour suppressor phosphatase and tensin homologue (PTEN) and promoted nuclear translocation of NF\u2010\u03baB p65, a known inhibitor of PTEN transcription. Consistent with these findings, HS tissues exhibited elevated DDR1 expression and reduced PTEN levels relative to adjacent normal skin. The pathological role of DDR1 in HS was further validated in a rabbit ear model, in which local administration of a selective DDR1 inhibitor significantly attenuated scar formation. Together, these findings delineated a collagen III\u2010DDR1\u2010PTEN signalling axis that drives fibroblast proliferation and activation in hypertrophic scarring, highlighting DDR1 as a promising therapeutic target for the prevention and treatment of HS.<\/jats:p>","DOI":"10.1111\/wrr.70221","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:29:37Z","timestamp":1791289777000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Collagen Receptor\n                    <scp>DDR1<\/scp>\n                    Drives Fibroblast Proliferation in Hyperplastic Scarring"],"prefix":"10.1111","volume":"34","author":[{"given":"Lifeng","family":"Guan","sequence":"first","affiliation":[{"name":"Basic Medical Sciences College, Ningxia Medical University  Yinchuan People's Republic of China"},{"name":"Department of Burns and Plastic Surgery General Hospital, Ningxia Medical University  Yinchuan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Ding","sequence":"additional","affiliation":[{"name":"Basic Medical Sciences College, Ningxia Medical University  Yinchuan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjie","family":"Hao","sequence":"additional","affiliation":[{"name":"Basic Medical Sciences College, Ningxia Medical University  Yinchuan People's Republic of China"},{"name":"Ningxia Clinical Research Institute, People's Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University  Yinchuan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wang","sequence":"additional","affiliation":[{"name":"Basic Medical Sciences College, Ningxia Medical University  Yinchuan People's Republic of China"},{"name":"Ningxia Clinical Research Institute, People's Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University  Yinchuan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Dong","sequence":"additional","affiliation":[{"name":"Basic Medical Sciences College, Ningxia Medical University  Yinchuan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9701-6592","authenticated-orcid":false,"given":"Hongning","family":"Ma","sequence":"additional","affiliation":[{"name":"Ningxia Clinical Research Institute, People's Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University  Yinchuan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5245-1351","authenticated-orcid":false,"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Basic Medical Sciences College, Ningxia Medical University  Yinchuan People's Republic of China"},{"name":"Ningxia Clinical Research Institute, People's Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University  Yinchuan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"issue":"3","key":"e_1_2_9_2_1","article-title":"Medical Needling: Effect on Moisture and Transepidermal Water Loss of Mature Hypertrophic Burn Scars","volume":"10","author":"Busch K. H.","year":"2018","journal-title":"Cureus"},{"key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1007\/s10103-018-2562-1","article-title":"Evaluation of the Therapeutic Effect of Micro\u2010Plasma Radio Frequency on Hypertrophic Scars in Rabbit Ears","volume":"33","author":"Zhang W.","year":"2018","journal-title":"Lasers in Medical Science"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","DOI":"10.1177\/2059513117702162","article-title":"Intralesional Cryotherapy for Hypertrophic Scars and Keloids: A Review","volume":"3","author":"O'Boyle C. P.","year":"2017","journal-title":"Scars Burns Healing"},{"issue":"2","key":"e_1_2_9_5_1","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1111\/exd.12601","article-title":"Periostin Induces Fibroblast Proliferation and Myofibroblast Persistence in Hypertrophic Scarring","volume":"24","author":"Crawford J.","year":"2015","journal-title":"Experimental Dermatology"},{"key":"e_1_2_9_6_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/B978-0-12-800180-6.00002-5","article-title":"Discoidin Domain Receptor Functions in Physiological and Pathological Conditions","volume":"310","author":"Leitinger B.","year":"2014","journal-title":"International Review of Cell and Molecular Biology"},{"issue":"4","key":"e_1_2_9_7_1","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.jid.2024.08.013","article-title":"Type III Collagen Regulates Matrix Architecture and Mechanosensing During Wound Healing","volume":"145","author":"Stewart D. C.","year":"2025","journal-title":"Journal of Investigative Dermatology"},{"issue":"1","key":"e_1_2_9_8_1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.matbio.2010.10.004","article-title":"Collagen Binding Specificity of the Discoidin Domain Receptors: Binding Sites on Collagens II and III and Molecular Determinants for Collagen IV Recognition by DDR1","volume":"30","author":"Xu H.","year":"2011","journal-title":"Matrix Biology"},{"issue":"1","key":"e_1_2_9_9_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1002\/path.5969","article-title":"Glomerular Basement Membrane Deposition of Collagen alpha1(III) in Alport Glomeruli by Mesangial Filopodia Injures Podocytes via Aberrant Signaling Through DDR1 and Integrin alpha2beta1","volume":"258","author":"Madison J.","year":"2022","journal-title":"Journal of Pathology"},{"issue":"3","key":"e_1_2_9_10_1","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1128\/MCB.24.3.1007-1021.2004","article-title":"Suppression of PTEN Expression by NF\u2010Kappa B Prevents Apoptosis","volume":"24","author":"Vasudevan K. M.","year":"2004","journal-title":"Molecular and Cellular Biology"},{"issue":"26","key":"e_1_2_9_11_1","doi-asserted-by":"crossref","first-page":"40025","DOI":"10.18632\/oncotarget.9474","article-title":"Higher Methylation Intensity Induced by EBV LMP1 via NF\u2010kappaB\/DNMT3b Signaling Contributes to Silencing of PTEN Gene","volume":"7","author":"Peng H.","year":"2016","journal-title":"Oncotarget"},{"issue":"1","key":"e_1_2_9_12_1","first-page":"S40","article-title":"Hypertrophic Scar Model in the Rabbit Ear: A Reproducible Model for Studying Scar Tissue Behavior With New Observations on Silicone Gel Sheeting for Scar Reduction","volume":"15","author":"Kloeters O.","year":"2007","journal-title":"Wound Repair and Regeneration"},{"key":"e_1_2_9_13_1","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1016\/j.biopha.2018.06.103","article-title":"Naringin Suppresses the Growth and Motility of Hypertrophic Scar Fibroblasts by Inhibiting the Kinase Activity of Akt","volume":"105","author":"Song Y.","year":"2018","journal-title":"Biomedicine and Pharmacotherapy\/Biomedecine and Pharmacotherapie"},{"issue":"4","key":"e_1_2_9_14_1","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.cps.2017.05.008","article-title":"A Systematic Review of the Effectiveness of Laser Therapy for Hypertrophic Burn Scars","volume":"44","author":"Zuccaro J.","year":"2017","journal-title":"Clinics in Plastic Surgery"},{"issue":"6","key":"e_1_2_9_15_1","doi-asserted-by":"crossref","first-page":"751","DOI":"10.3346\/jkms.2014.29.6.751","article-title":"Overview of Surgical Scar Prevention and Management","volume":"29","author":"Son D.","year":"2014","journal-title":"Journal of Korean Medical Science"},{"issue":"1","key":"e_1_2_9_16_1","doi-asserted-by":"crossref","DOI":"10.1080\/19381980.2018.1448327","article-title":"The Pivotal Role of Inflammation in Scar\/Keloid Formation After Acne","volume":"9","author":"Shi C.","year":"2017","journal-title":"Dermato\u2010Endocrinology"},{"issue":"5","key":"e_1_2_9_17_1","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1111\/j.1524-475X.2009.00534.x","article-title":"Homeostasis of the Epidermal Barrier Layer: A Theory of How Occlusion Reduces Hypertrophic Scarring","volume":"17","author":"O'Shaughnessy K. D.","year":"2009","journal-title":"Wound Repair and Regeneration: Official Publication of the Wound Healing Society [and] the European Tissue Repair Society"},{"issue":"6","key":"e_1_2_9_18_1","first-page":"2998","article-title":"HOXA9 Regulates Angiogenesis in Human Hypertrophic Scars: Induction of VEGF Secretion by Epidermal Stem Cells","volume":"7","author":"Cao P. F.","year":"2014","journal-title":"International Journal of Clinical and Experimental Pathology"},{"issue":"14","key":"e_1_2_9_19_1","doi-asserted-by":"crossref","first-page":"12384","DOI":"10.1074\/jbc.M208544200","article-title":"Myofibroblast Differentiation by Transforming Growth Factor\u2010beta1 Is Dependent on Cell Adhesion and Integrin Signaling via Focal Adhesion Kinase","volume":"278","author":"Thannickal V. J.","year":"2003","journal-title":"Journal of Biological Chemistry"},{"key":"e_1_2_9_20_1","first-page":"301","article-title":"Fibroblasts and Myofibroblasts in Wound Healing","volume":"7","author":"Darby I. A.","year":"2014","journal-title":"Clinical, Cosmetic and Investigational Dermatology"},{"issue":"2","key":"e_1_2_9_21_1","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/ki.2014.287","article-title":"Origin of Myofibroblasts and Cellular Events Triggering Fibrosis","volume":"87","author":"Mack M.","year":"2015","journal-title":"Kidney International"},{"issue":"32","key":"e_1_2_9_22_1","first-page":"E3297","article-title":"Origin of Myofibroblasts in the Fibrotic Liver in Mice","volume":"111","author":"Iwaisako K.","year":"2014","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"e_1_2_9_23_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2025.156498","article-title":"Artesunate Attenuates Skin Hypertrophic Scar Formation by Inhibiting Fibroblast Activation and EndMT of Vascular Endothelial Cells","volume":"140","author":"Shang R. Y.","year":"2025","journal-title":"Phytomedicine"},{"issue":"10","key":"e_1_2_9_24_1","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1016\/j.bbapap.2012.10.014","article-title":"Collagen Recognition and Transmembrane Signalling by Discoidin Domain Receptors","volume":"1834","author":"Carafoli F.","year":"2013","journal-title":"Biochimica et Biophysica Acta"},{"issue":"2","key":"e_1_2_9_25_1","first-page":"134","article-title":"Discoidin Domain Receptors (DDRs) Expression in Pathological Scar Fibroblast Formation","volume":"23","author":"Jiang Y. Z.","year":"2007","journal-title":"Zhonghua Zheng Xing Wai Ke Za Zhi = Zhonghua Zhengxing Waike Zazhi = Chinese Journal of Plastic Surgery"},{"issue":"1","key":"e_1_2_9_26_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1097\/01.ASW.0000547415.38888.c4","article-title":"Duration of Scar Maturation: Retrospective Analyses of 361 Hypertrophic Scars Over 5\u2009Years","volume":"32","author":"Kant S.","year":"2019","journal-title":"Advances in Skin and Wound Care"},{"key":"e_1_2_9_27_1","doi-asserted-by":"crossref","first-page":"2869","DOI":"10.1007\/s11033-018-4321-6","article-title":"Regulation and Modulation of PTEN Activity","volume":"45","author":"Naderali E.","year":"2018","journal-title":"Molecular Biology Reports"},{"issue":"3","key":"e_1_2_9_28_1","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.cmet.2014.01.019","article-title":"Cholesteryl Ester Accumulation Induced by PTEN Loss and PI3K\/AKT Activation Underlies Human Prostate Cancer Aggressiveness","volume":"19","author":"Yue S.","year":"2014","journal-title":"Cell Metabolism"},{"issue":"5","key":"e_1_2_9_29_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0097114","article-title":"MicroRNA\u201021 Regulates hTERT via PTEN in Hypertrophic Scar Fibroblasts","volume":"9","author":"Zhu H. Y.","year":"2014","journal-title":"PLoS One"},{"issue":"1","key":"e_1_2_9_30_1","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s11010-011-1100-2","article-title":"PTEN Inhibits Proliferation and Functions of Hypertrophic Scar Fibroblasts","volume":"361","author":"Guo L.","year":"2012","journal-title":"Molecular and Cellular Biochemistry"}],"container-title":["Wound Repair and Regeneration"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/wrr.70221","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/wrr.70221","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/wrr.70221","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:29:41Z","timestamp":1791289781000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/wrr.70221"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":29,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1111\/wrr.70221"],"URL":"https:\/\/doi.org\/10.1111\/wrr.70221","archive":["Portico"],"relation":{},"ISSN":["1067-1927","1524-475X"],"issn-type":[{"value":"1067-1927","type":"print"},{"value":"1524-475X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-04-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70221"}}