The role of alpha1beta1 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 alpha1beta1 and alpha2beta1, 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 alpha1 and alpha2 integrin subunits during the in vivo injury. Normal stellate cells displayed alpha1 but no detectable alpha2. During injury, alpha1 expression was maintained; alpha2 became detectable at the mRNA level but at all times was <8% of alpha1 mRNA. Contraction of collagen lattices, studied with 24-h cultured cells and initiated by endothelin 1, was blocked 70% by anti-alpha1 and 30% by anti-alpha2 (both significant, p < 0.05). The inhibition by anti-alpha2, which was unexpected, was attributable to culture-induced change in integrin expression; both the mRNA and protein for alpha2 increased strikingly within 24 h of plating stellate cells on a collagen gel. We conclude that alpha1beta1 is the sole integrin utilized by contracting myofibroblasts in vivo. Although alpha2beta1 is capable of mediating contraction, its expression by myofibroblasts occurs largely, if not exclusively, in response to culture.
Racine-Samson
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Liver Center Laboratory, San Francisco General Hospital, and the Department of Medicine, University of California, San Francisco, California 94110, USA.
Rockey
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Bissell
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D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology*; D039423:Integrin alpha1; D039222:Integrin alpha1beta1; D039421:Integrin alpha2; D019012:Integrin beta1 / Q000502:physiology*; D016023:Integrins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000166:cytology*; D009132:Muscles / Q000166:cytology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D039423:Integrin alpha1; D039222:Integrin alpha1beta1; D039421:Integrin alpha2; D019012:Integrin beta1; D016023:Integrins; D012333:RNA, Messenger; D003094:Collagen