Specific inhibition of human skin fibroblast chemotaxis to platelet-derived growth factor A-chain homodimer by transforming growth factor-beta1

Arch Dermatol Res. 2002 Feb;293(12):609-13. doi: 10.1007/s00403-001-0279-6. Epub 2002 Jan 23.

Abstract

Platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) have been suggested to play important roles in wound healing. We investigated the effect of TGF-beta1 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-beta1 inhibited the growth-promoting activity of both PDGFs. Proliferative responses to basic fibroblast growth factor and epidermal growth factor were also restricted by TGF-beta1. A Boyden chamber chemotaxis assay revealed that the chemotactic migration to PDGF-AA was inhibited by TGF-beta1 pretreatment, but in contrast, the response to PDGF-BB was not affected by the same treatment. Western blot analysis showed that TGF-beta1 downregulated PDGF alpha-receptors, but not beta-receptors, indicating that the isoform-specific inhibition of chemotaxis is related to differential effects of TGF-beta1 on PDGF receptor expression. The present findings suggest that TGF-beta1 may act antagonistically towards PDGFs in humans under certain conditions, and this antagonistic nature of TGF-beta1 must be considered when it is applied to human wounds as a therapeutic agent.

MeSH terms

  • Cell Division / drug effects
  • Cells, Cultured
  • Chemotaxis / drug effects*
  • Dimerization
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / physiology*
  • Humans
  • Mitogens / antagonists & inhibitors
  • Mitogens / pharmacology
  • Platelet-Derived Growth Factor / antagonists & inhibitors
  • Platelet-Derived Growth Factor / chemistry
  • Platelet-Derived Growth Factor / pharmacology*
  • Receptors, Platelet-Derived Growth Factor / metabolism
  • Skin Physiological Phenomena*
  • Transforming Growth Factor beta / pharmacology*
  • Transforming Growth Factor beta1

Substances

  • Mitogens
  • Platelet-Derived Growth Factor
  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • platelet-derived growth factor A
  • Receptors, Platelet-Derived Growth Factor