The role of α1β1 integrin in wound contraction.: A quantitative analysis of liver myofibroblasts in vivo and in primary culture.

An unresolved question in wound contraction concerns the identity of integrins mediating the attachment of tissue myofibroblasts to matrix in the injury site. Previous studies with cell lines have focussed on alpha 1 beta 1 and alpha 2 beta 1, the principal collagen-binding integrins, but have yielded conflicting data. We have examined this issue in wound healing in the liver, isolating the myofibroblast population (activated stellate cells) and quantitating expression of the alpha 1 and alpha 2 integrin subunits during the in vivo injury. Normal stellate cells displayed alpha 1 but no detectable alpha 2. During injury, alpha 1 expression was maintained; alpha 2 became detectable at the mRNA level but at all times was <8% of alpha 1 mRNA. Contraction of collagen lattices, studied with 24-h cultured cells and initiated by endothelin 1, was blocked 70% by anti-alpha 1 and 30% by anti-alpha 2 (both significant, p < 0.05). The inhibition by anti-alpha 2, which was unexpected, was attributable to culture-induced change in integrin expression; both the mRNA and protein for alpha 2 increased strikingly within 24 h of plating stellate cells on a collagen gel. We conclude that alpha 1 beta 1 is the sole integrin utilized by contracting myofibroblasts in vivo. Although alpha 2 beta 1 is capable of mediating contraction, its expression by myofibroblasts occurs largely, if not exclusively, in response to culture.