Specific inhibition of human skin fibroblast chemotaxis to platelet-derived growth factor A-chain homodimer by transforming growth factor-beta1.
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.
Soma
Yoshinao
Y
Department of Dermatology, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kawasaki 216-8511, Japan.
Mizoguchi
Masako
M
Yamane
Kenichi
K
Yazawa
Norihito
N
Kubo
Masahide
M
Ihn
Hironobu
H
Kikuchi
Kanako
K
Tamaki
Kunihiko
K
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects*; D019281:Dimerization; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008934:Mitogens / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D012879:Skin Physiological Phenomena; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
D008934:Mitogens; D010982:Platelet-Derived Growth Factor; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C075278:platelet-derived growth factor A; D017479:Receptors, Platelet-Derived Growth Factor