Dermal αSMA+ myofibroblasts orchestrate skin wound repair via β1 integrin and independent of type I collagen production

Kathleen M. McAndrews, Toru Miyake, Ehsan A. Ehsanipour, Patience J. Kelly, Lisa M. Becker, Daniel James McGrail, Hikaru Sugimoto, Valerie LeBleu, Yejing Ge, Raghu Kalluri

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Skin wound repair is essential for organismal survival and failure of which leads to non-healing wounds, a leading health issue worldwide. However, mechanistic understanding of chronic wounds remains a major challenge due to lack of appropriate genetic mouse models. αSMA+ myofibroblasts, a unique class of dermal fibroblasts, are associated with cutaneous wound healing but their precise function remains unknown. We demonstrate that genetic depletion of αSMA+ myofibroblasts leads to pleiotropic wound healing defects, including lack of reepithelialization and granulation, dampened angiogenesis, and heightened hypoxia, hallmarks of chronic non-healing wounds. Other wound-associated FAP+ and FSP1+ fibroblasts do not exhibit such dominant functions. While type I collagen (COL1) expressing cells play a role in the repair process, COL1 produced by αSMA+ myofibroblasts is surprisingly dispensable for wound repair. In contrast, we show that β1 integrin from αSMA+ myofibroblasts, but not TGFβRII, is essential for wound healing, facilitating contractility, reepithelization, and vascularization. Collectively, our study provides evidence for the functions of myofibroblasts in β1 integrin-mediated wound repair with potential implications for treating chronic non-healing wounds.

Original languageEnglish (US)
Article numbere109470
JournalEMBO Journal
Volume41
Issue number7
DOIs
StatePublished - Apr 4 2022

Keywords

  • extracellular matrix
  • myofibroblasts
  • wound healing

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

MD Anderson CCSG core facilities

  • Advanced Technology Genomics Core

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