BMP-7 does not protect against bleomycin-induced lung or skin fibrosis

PLoS One. 2008;3(12):e4039. doi: 10.1371/journal.pone.0004039. Epub 2008 Dec 29.

Abstract

Bone morphogenic protein (BMP)-7 is a member of the BMP family which are structurally and functionally related, and part of the TGFbeta super family of growth factors. BMP-7 has been reported to inhibit renal fibrosis and TGFbeta1-induced epithelial-mesenchymal transition (EMT), in part through negative interactions with TGFbeta1 induced Smad 2/3 activation. We utilized in vivo bleomycin-induced fibrosis models in the skin and lung to determine the potential therapeutic effect of BMP-7. We then determined the effect of BMP-7 on TGFbeta1-induced EMT in lung epithelial cells and collagen production by human lung fibroblasts. We show that BMP-7 did not affect bleomycin-induced fibrosis in either the lung or skin in vivo; had no effect on expression of pro-fibrotic genes by human lung fibroblasts, either at rest or following exposure to TGFbeta1; and did not modulate TGFbeta1-induced EMT in human lung epithelial cells. Taken together our data indicates that BMP-7 has no anti-fibrotic effect in lung or skin fibrosis either in vivo or in vitro. This suggests that the therapeutic options for BMP-7 may be confined to the renal compartment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bleomycin / pharmacology*
  • Bone Morphogenetic Protein 7 / metabolism
  • Bone Morphogenetic Protein 7 / physiology*
  • Disease Models, Animal
  • Epithelial Cells / metabolism
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibrosis / chemically induced*
  • Fibrosis / metabolism*
  • Gene Expression Regulation*
  • Humans
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Skin / drug effects
  • Skin / pathology*
  • Smad2 Protein / metabolism
  • Smad3 Protein / metabolism

Substances

  • Bone Morphogenetic Protein 7
  • SMAD2 protein, human
  • SMAD3 protein, human
  • Smad2 Protein
  • Smad3 Protein
  • Bleomycin