Selective modulation of collagen gene expression by different isoforms of platelet-derived growth factor in experimental wound healing.

Subcutaneous sponges in rat were used as a wound model to study the changes in collagen gene expression induced by different isoforms of platelet-derived growth factor (PDGF). The steady state levels of proalpha1(I) and proalpha1(III) collagens rose markedly in response to PDGF-AB treatment. In marked contrast to PDGF-AB, PDGF-BB exerted a down-regulatory effect on the expression of type I and III procollagen mRNA levels. In situ hybridisation signal for proalpha1(I) collagen mRNA was most prominent in the periphery of the sponges in response to PDGF-AB. In PDGF-AA and PDGF-BB treated sponges, however, the hybridisation signal for proalpha1(I) collagen mRNA was evenly distributed. Immunolabellings demonstrated the presence of type I and III collagen epitopes and thus revealed the deposition of these proteins into developing granulation tissue. The volume of ingrown granulation tissue was estimated by measuring the cross-sectional area of the samples. PDGF-AB and PDGF-BB were both effective resulting in a significant increase in the amount of granulation tissue. However, only a limited enhancement of granulation tissue ingrowth was observed in response to PDGF-AA treatment. To conclude, PDGF-AB and PDGF-BB induced significantly the ingrowth of repair tissue in wounds. PDGF-AB distinctively upregulated collagen gene expression, while PDGF-BB primarily seemed to be mitogenic.