Nephrol Dial Transplant (2000) 15: 1766-1772
© 2000 European Renal Association-European Dialysis and Transplant Association
Human renal fibroblast contraction of collagen I lattices is an integrin-mediated process
1 Department of Nephrology, Royal Melbourne Hospital, Parkville and 2 Microvascular Biology and Wound Healing Group, RMIT University, Bundoora, Victoria, Australia
Background. Expression of the ß1 family of integrins allows dermal fibroblasts in wounds to contribute to the healing process through migration, adhesion, synthesis, and rearrangement of extracellular matrix. To date the ability of human renal fibroblasts to reorganize collagens and the role of cell surface receptors in this process remain unknown.
Methods. Renal fibroblasts were grown from the cortical tissue of surgically removed human kidneys. The ability of human renal fibroblasts to reorganize interstitial collagen I was examined in vitro using solidified collagen I lattices. Integrin function was blocked by incubating fibroblasts with isotype-specific antibodies prior to addition to collagen I lattices.
Results. Human renal fibroblasts embedded in collagen I lattices progressively 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 ß1 integrin failed to contract collagen I lattices, whilst fibroblasts incubated with non-specific antibody reduced lattice diameter to 60.1±12.4% of initial diameter at 48 h post-release (P<0.01). Further characterization of integrin 
subunits showed that blocking 2ß1 integrin prevented lattice contraction (P<0.05, 2ß1 integrin antibody vs non-specific antibody), whilst blocking of 5ß1, 3ß1 and 1ß1 integrins did not influence this process.
Conclusions.We postulate that collagen I fibril rearrangement by human renal fibroblasts in vitro appears to be an integrin-mediated process involving the 2ß1 integrin.
Keywords: collagen lattices; contraction; fibroblast; integrin; renal; scar formation
Correspondence and offprint requests to: Tim D. Hewitson, Department of Nephrology, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
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