BMP-7 does not protect against bleomycin-induced lung or skin fibrosis.
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.
Murray
Lynne A
LA
Immunobiology Department, Centocor, Radnor, Pennsylvania, USA. lmurray@promedior.com
Hackett
Tillie L
TL
Warner
Stephanie M
SM
Shaheen
Furquan
F
Argentieri
Rochelle L
RL
Dudas
Paul
P
Farrell
Francis X
FX
Knight
Darryl A
DA
D000818:Animals; D001761:Bleomycin / Q000494:pharmacology*; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism / Q000502:physiology*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005355:Fibrosis / Q000139:chemically induced* / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012867:Skin / Q000187:drug effects / Q000473:pathology*; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism
D055419:Bone Morphogenetic Protein 7; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D001761:Bleomycin