Absence of integrin alpha1beta1 in the mouse causes loss of feedback regulation of collagen synthesis in normal and wounded dermis.
Integrin alpha1beta1 is a collagen receptor predominantly found in mesenchymal tissues. Mice lacking this receptor are viable. We have previously suggested that alpha1beta1 might participate in the down-regulation of collagen gene expression observed in cells suspended inside collagen gels. The results presented here demonstrate that integrin alpha1beta1 acts as a feedback regulator of collagen synthesis both in vitro and in vivo. Firstly, alpha1 null animals show a higher rate of collagen synthesis in the dermis in vivo. Secondly, fibroblasts derived from alpha1 null cutaneous wounds show a reduced sensitivity to collagen gel induced downregulation of collagen mRNA synthesis, as compared to their wild-type counterparts. An increase in collagenase synthesis is also seen in the alpha1 null dermis and in collagen gel suspended fibroblasts. While dermal thickness is normal in the alpha1 null animals, an increase is seen in skin thickness of alpha1 null but not alpha1 heterozygote animals on a background of collagenase resistant collagen. Increased expression of both collagen and collagenase mRNA are seen in experimental granulation tissue in alpha1 null animals, but their ultimate accumulation of collagen is normal, probably due to non alpha1 dependent paracrine regulators of collagen turnover.
Gardner
H
H
Department of Cell Biology, The Scripps Research Institute, La Jolla, California USA 92037, USA. humphrey@scripps.edu
Broberg
A
A
Pozzi
A
A
Laato
M
M
Heino
J
J
D000818:Animals; D002460:Cell Line; D003094:Collagen / Q000096:biosynthesis* / Q000378:metabolism; D020405:Dermis / Q000293:injuries* / Q000378:metabolism*; D015536:Down-Regulation; D005246:Feedback; D005347:Fibroblasts / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006097:Granulation Tissue / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D039222:Integrin alpha1beta1; D016023:Integrins / Q000502:physiology*; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism
D039222:Integrin alpha1beta1; D016023:Integrins; D012333:RNA, Messenger; D003094:Collagen; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D006909:Hydroxyproline