| First Author | Longmate WM | Year | 2014 |
| Journal | J Invest Dermatol | Volume | 134 |
| Issue | 6 | Pages | 1609-1617 |
| PubMed ID | 24390135 | Mgi Jnum | J:210857 |
| Mgi Id | MGI:5571984 | Doi | 10.1038/jid.2014.10 |
| Citation | Longmate WM, et al. (2014) Reduced fibulin-2 contributes to loss of basement membrane integrity and skin blistering in mice lacking integrin alpha3beta1 in the epidermis. J Invest Dermatol 134(6):1609-17 |
| abstractText | Deficient epidermal adhesion is a hallmark of blistering skin disorders and chronic wounds, implicating integrins as potential therapeutic targets. Integrin alpha3beta1, a major receptor in the epidermis for adhesion to laminin-332 (LN-332), has critical roles in basement membrane (BM) organization during skin development. In the current study we identify a role for alpha3beta1 in promoting stability of nascent epidermal BMs through induction of fibulin-2, a matrix-associated protein that binds LN-332. We demonstrate that mice lacking alpha3beta1 in the epidermis display ruptured BM beneath neo-epidermis of wounds, characterized by extensive blistering. This junctional blistering phenocopies defects reported in newborn alpha3-null mice, as well as in human patients with alpha3 gene mutations, indicating that the developmental role of alpha3beta1 in BM organization is recapitulated during wound healing. Mice lacking epidermal alpha3beta1 also have reduced fibulin-2 expression, and fibulin-2-null mice display perinatal skin blisters similar to those in alpha3beta1-deficient mice. Interestingly, alpha3-null wound epidermis or keratinocytes also show impaired processing of the LN-332 gamma2 chain, although this defect was independent of reduced fibulin-2 and did not appear to cause blistering. Our findings indicate a role for integrin alpha3beta1 in BM stability through fibulin-2 induction, both in neonatal skin and in adult wounds. |
