Opposing Roles of Epidermal Integrins ?3?1 and ?9?1 in Regulation of mTLD/BMP-1-Mediated Laminin-?2 Processing during Wound Healing.

ABSTRACT: Proteolytic processing of the laminin-?2 chain is a hallmark of basement membrane maturation in the skin. Integrin ?3?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 ?3?1 in promoting the processing of laminin-?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 ?3?1-dependent laminin-?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, ?9?1, as a suppressive regulator of ?3?1-dependent wound angiogenesis, we investigated whether ?9?1 has a similar cross-suppressive effect on the ability of ?3?1 to promote basement membrane organization. Here, we show that, rather than a cross-suppressive role, ?9?1 has an opposing role in basement membrane assembly/maturation through reduced laminin-?2 processing via mTLD/BMP-1. Although ?3?1 promotes this process during wound healing, ?9?1 has an inhibitory role, suggesting that regulation of basement membrane assembly requires a complex interplay between these distinct epidermal integrins.

SUBMITTER: Longmate WM 

PROVIDER: S-EPMC5794664 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature