Regulation of fibrogenic/fibrolytic genes by platelet-derived growth factor C, a novel growth factor, in human dermal fibroblasts

J Cell Physiol. 2005 Feb;202(2):510-7. doi: 10.1002/jcp.20154.


Platelet-derived growth factor (PDGF) is a potent mitogenic and chemotactic cytokine, and PDGF-C is a novel growth factor belonging to the PDGF family. In this study, to determine whether this growth factor can contribute to fibrosis and tissue remodeling, we examined the effect of PDGF-CC on the expression of fibrogenic/fibrolytic genes such as type I collagen, fibronectin (FN), matrix metalloproteinases (MMPs), and their inhibitors (TIMPs) in normal human dermal fibroblasts in vitro. PDGF elevated the levels of MMP-1 or TIMP-1 protein as well as mRNA, whereas this cytokine had no influence on the expression of type I collagen, FN, or TIMP-2. PDGF-CC also increased the levels of MMP-1 catalytic activity in the cultured media and mRNA expression, which was paralleled that on the levels of promoter activation. Additionally, PDGF-CC induced the mitogenic and migratory activity of human dermal fibroblasts in a dose-dependent manner. On the other hand, we also determined the specificity of the inhibitory effect of monoclonal antibodies against PDGF-CC generated by immunizing balb/c mice with recombinant human PDGF-CC. This antibody could inhibit the regulatory effects of MMP-1 or TIMP-1 synthesis as well as the mitogenic effects on human dermal fibroblasts induced by PDGF-CC, whereas this antibody did not affect those induced by other PDGF forms such as PDGF-AA, -AB, or -BB. These results suggest that this cytokine plays a role in the tissue remodeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Cell Movement / drug effects
  • Cells, Cultured
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Fibroblasts / physiology*
  • Fibronectins / genetics
  • Fibronectins / metabolism
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Humans
  • Lymphokines
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mitogens / pharmacology
  • Platelet-Derived Growth Factor / immunology
  • Platelet-Derived Growth Factor / pharmacology
  • Platelet-Derived Growth Factor / physiology*
  • Promoter Regions, Genetic / drug effects
  • RNA, Messenger / metabolism
  • Recombinant Proteins / pharmacology
  • Skin / cytology
  • Skin Physiological Phenomena*
  • Tissue Inhibitor of Metalloproteinases / genetics
  • Tissue Inhibitor of Metalloproteinases / metabolism


  • Antibodies, Monoclonal
  • Collagen Type I
  • Fibronectins
  • Lymphokines
  • Mitogens
  • Platelet-Derived Growth Factor
  • RNA, Messenger
  • Recombinant Proteins
  • Tissue Inhibitor of Metalloproteinases
  • platelet-derived growth factor C
  • Matrix Metalloproteinases