Pro-fibrogenic potential of PDGF-D in liver fibrosis

J Hepatol. 2007 Jun;46(6):1064-74. doi: 10.1016/j.jhep.2007.01.029. Epub 2007 Feb 23.


Background/aims: We analyzed the expression of platelet-derived growth factor D (PDGF-D) in an experimental bile duct-ligated (BDL) rat model and assessed its biological function in cultured hepatic stellate cells (HSC) and myofibroblasts (MFB).

Methods: The mRNA for PDGF-A, -B, -C, -D and for PDGF receptor-alpha and -beta chains (PDGFRalpha and PDGFRbeta) in normal and fibrotic rat livers was assessed quantitatively. Protein levels of PDGF-D were quantified by immunoblotting and immunohistochemistry.

Results: The relative mRNA expression of all PDGF isoforms and receptors upregulated upon BDL and PDGF-A, -B and -D expression was significantly higher than that of PDGF-C. PDGF-D and PDGFRbeta protein also increased markedly. Immunostaining revealed that PDGF-D is localized along the fibrotic septa of the periportal- and perisinusoidal areas. Besides PDGF-B, PDGF-D is the second most potent PDGF isoform in PDGFRbeta signaling within HSC/MFB, evidenced by PDGFRbeta autophosphorylation and activation of the downstream signaling molecules ERK1/2-, JNK-, p38 MAPK, and PKB/Akt while PDGF-C effects were minimal. PDGF-D exerted mitogenic and fibrogenic effects in both cultured HSC and MFB comparable to PDGF-B but PDGF-A and -C showed only marginal fibrogenic effects.

Conclusions: PDGF-D possesses potential pathogenetic properties for HSC activation and matrix remodeling in liver fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Cytosol / metabolism
  • DNA Primers / chemistry
  • Fibroblasts / metabolism
  • Ligands
  • Liver / cytology
  • Liver / metabolism*
  • Liver / pathology*
  • Liver Cirrhosis / pathology*
  • Lymphokines / metabolism
  • Lymphokines / physiology*
  • Male
  • Platelet-Derived Growth Factor / metabolism
  • Platelet-Derived Growth Factor / physiology*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction


  • DNA Primers
  • Ligands
  • Lymphokines
  • Pdgfd protein, rat
  • Platelet-Derived Growth Factor
  • RNA, Messenger