Human renal fibroblast contraction of collagen I lattices is an integrin-mediated process

Background. Expression of the beta1 family of integrins allows dermal fibro blasts in wounds to contribute to the healing process through migration, ad hesion, synthesis, and rearrangement of extracellular matrix. To date the a bility of human renal fibroblasts to reorganize collagens and the role of c ell surface receptors in this process remain unknown. Methods. Renal fibroblasts were grown from the cortical tissue of surgicall y removed human kidneys. The ability of human renal fibroblasts to reorgani ze interstitial collagen I was examined in vitro using solidified collagen I lattices. Integrin function was blocked by incubating fibroblasts with is otype-specific antibodies prior to addition to collagen I lattices. Results. Human renal fibroblasts embedded in collagen 1 lattices progressiv ely decreased lattice diameter to 60.6+/-11.4% of initial diameter at 48 h post-release (P<0.01). Fibroblasts incubated in the presence of antibody to <beta>1 integrin failed to contract collagen I lattices. whilst fibroblast s incubated with non-specific antibody reduced lattice diameter to 60.1+/-1 2.4% of initial diameter at 48 h post-release (P < 0.01). Further character ization of integrin a subunits showed that blocking <alpha>2 beta1 integrin prevented lattice contraction (P<0.05, <alpha>2 beta1 integrin antibody vs non-specific antibody), whilst blocking of alpha5 beta1, alpha3 beta1 and alpha1 beta1 integrins did not influence this process. Conclusions. We postulate that collagen I fibril rearrangement by human ren al fibroblasts in vitro appears to be an integrin-mediated process involvin g the alpha2 beta1 integrin.