Specific inhibition of human skin fibroblast chemotaxis to platelet-derived growth factor A-chain homodimer by transforming growth factor-β1

Abstract

Platelet-derived growth factor (PDGF) and transforming growth factor-β (TGF-β) have been suggested to play important roles in wound healing. We investigated the effect of TGF-β1 on the mitogenic and chemotactic activities of PDGF A-chain homodimer (PDGF-AA) and B-chain homodimer (PDGF-BB) in primary cultures of human skin fibroblasts. TGF-β1 inhibited the growth-promoting activity of both PDGFs. Proliferative responses to basic fibroblast growth factor and epidermal growth factor were also restricted by TGF-β1. A Boyden chamber chemotaxis assay revealed that the chemotactic migration to PDGF-AA was inhibited by TGF-β1 pretreatment, but in contrast, the response to PDGF-BB was not affected by the same treatment. Western blot analysis showed that TGF-β1 downregulated PDGF α-receptors, but not β-receptors, indicating that the isoform-specific inhibition of chemotaxis is related to differential effects of TGF-β1 on PDGF receptor expression. The present findings suggest that TGF-β1 may act antagonistically towards PDGFs in humans under certain conditions, and this antagonistic nature of TGF-β1 must be considered when it is applied to human wounds as a therapeutic agent.