4.7 Article

Opposing Roles of Epidermal Integrins alpha 3 beta 1 and alpha 9 beta 1 in Regulation of mTLD/BMP-1-Mediated Laminin-gamma(2) Processing during Wound Healing

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JOURNAL OF INVESTIGATIVE DERMATOLOGY
卷 138, 期 2, 页码 444-451

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ELSEVIER SCIENCE INC
DOI: 10.1016/j.jid.2017.09.004

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资金

  1. National Institutes of Health grant from the National Institute of Arthritis and Musculoskeletal Diseases [R01AR063778]
  2. National Institutes of Health predoctoral fellowship from the National Cancer Institute [F31CA174198]
  3. NATIONAL CANCER INSTITUTE [F31CA174198] Funding Source: NIH RePORTER
  4. NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR063778] Funding Source: NIH RePORTER

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Proteolytic processing of the laminin-gamma(2) chain is a hallmark of basement membrane maturation in the skin. Integrin alpha 3 beta 1, a major receptor for epidermal adhesion to laminin-332, is critical for proper basement membrane organization during skin development and wound healing. Previously, we identified a role for alpha 3 beta 1 in promoting the processing of laminin-gamma(2) in cultured keratinocytes in vitro and in wound epidermis in vivo. In this study we identify the Bmp1 gene, which encodes variants of the mTLD/BMP-1 metalloproteases, as a critical regulator of alpha 3 beta 1-dependent laminin-gamma(2) processing, thereby expanding the role of this integrin in controlling the secretion by the epidermis of factors that modulate the tissue microenvironment. Because our previous studies identified another epidermal integrin, alpha 9 beta 1, as a suppressive regulator of alpha 3 beta 1-dependent wound angiogenesis, we investigated whether alpha 9 beta 1 has a similar cross-suppressive effect on the ability of alpha 3 beta 1 to promote basement membrane organization. Here, we show that, rather than a cross-suppressive role, alpha 9 beta 1 has an opposing role in basement membrane assembly/maturation through reduced laminin-gamma(2) processing via mTLD/ BMP-1. Although alpha 3 beta 1 promotes this process during wound healing, alpha 9 beta 1 has an inhibitory role, suggesting that regulation of basement membrane assembly requires a complex interplay between these distinct epidermal integrins.

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