Daniel C. Stewart , Becky K. Brisson , William K. Yen , Yuchen Liu , Chao Wang , Gordon Ruthel , Donald Gullberg , Robert L. Mauck , Malcolm Maden , Lin Han , Susan W. Volk
{"title":"Type III Collagen Regulates Matrix Architecture and Mechanosensing during Wound Healing","authors":"Daniel C. Stewart , Becky K. Brisson , William K. Yen , Yuchen Liu , Chao Wang , Gordon Ruthel , Donald Gullberg , Robert L. Mauck , Malcolm Maden , Lin Han , Susan W. Volk","doi":"10.1016/j.jid.2024.08.013","DOIUrl":null,"url":null,"abstract":"<div><div>Postnatal cutaneous wound healing is characterized by development of a collagen-rich scar lacking the architecture and functional integrity of unwounded tissue. Directing cell behaviors to efficiently heal wounds while minimizing scar formation remains a major wound management goal. In this study, we demonstrate type III collagen (COL3) as a critical regulator of re-epithelialization and scar formation during healing of COL3-enriched, regenerative (<em>Acomys</em>), scar-permissive (CD-1 <em>Mus</em> and wild-type <em>Col3</em><sup>B6/B6</sup> mice) and COL3-deficient, scar-promoting (<em>Col3</em><sup>F/F</sup>, a murine conditional knockdown model) cutaneous wound models. We define a scar-permissive fibrillar collagen architecture signature characterized by elongated and anisotropically aligned collagen fibers that is dose-dependently suppressed by COL3. Furthermore, loss of COL3 alters how cells interpret their microenvironment—their mechanoperception—such that COL3-deficient cells display mechanically active phenotypes in the absence of increased microenvironmental stiffness through the upregulation and engagement of the profibrotic integrin α11. Further understanding COL3’s role in regulating matrix architecture and mechanoresponses may inform clinical strategies that harness proregenerative mechanisms.</div></div>","PeriodicalId":16311,"journal":{"name":"Journal of Investigative Dermatology","volume":"145 4","pages":"Pages 919-938.e14"},"PeriodicalIF":5.7000,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Investigative Dermatology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0022202X24020785","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DERMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Postnatal cutaneous wound healing is characterized by development of a collagen-rich scar lacking the architecture and functional integrity of unwounded tissue. Directing cell behaviors to efficiently heal wounds while minimizing scar formation remains a major wound management goal. In this study, we demonstrate type III collagen (COL3) as a critical regulator of re-epithelialization and scar formation during healing of COL3-enriched, regenerative (Acomys), scar-permissive (CD-1 Mus and wild-type Col3B6/B6 mice) and COL3-deficient, scar-promoting (Col3F/F, a murine conditional knockdown model) cutaneous wound models. We define a scar-permissive fibrillar collagen architecture signature characterized by elongated and anisotropically aligned collagen fibers that is dose-dependently suppressed by COL3. Furthermore, loss of COL3 alters how cells interpret their microenvironment—their mechanoperception—such that COL3-deficient cells display mechanically active phenotypes in the absence of increased microenvironmental stiffness through the upregulation and engagement of the profibrotic integrin α11. Further understanding COL3’s role in regulating matrix architecture and mechanoresponses may inform clinical strategies that harness proregenerative mechanisms.
期刊介绍:
Journal of Investigative Dermatology (JID) publishes reports describing original research on all aspects of cutaneous biology and skin disease. Topics include biochemistry, biophysics, carcinogenesis, cell regulation, clinical research, development, embryology, epidemiology and other population-based research, extracellular matrix, genetics, immunology, melanocyte biology, microbiology, molecular and cell biology, pathology, percutaneous absorption, pharmacology, photobiology, physiology, skin structure, and wound healing