title: BMP-7 does not protect against bleomycin-induced lung or skin fibrosis.
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.
authors.affiliation: Immunobiology Department, Centocor, Radnor, Pennsylvania, USA. lmurray@promedior.com
authors.forename: Lynne A
authors.initials: LA
authors.lastname: Murray
authors.forename: Tillie L
authors.initials: TL
authors.lastname: Hackett
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Warner
authors.forename: Furquan
authors.initials: F
authors.lastname: Shaheen
authors.forename: Rochelle L
authors.initials: RL
authors.lastname: Argentieri
authors.forename: Paul
authors.initials: P
authors.lastname: Dudas
authors.forename: Francis X
authors.initials: FX
authors.lastname: Farrell
authors.forename: Darryl A
authors.initials: DA
authors.lastname: Knight
mesh_terms: 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
chemical_list: D055419:Bone Morphogenetic Protein 7; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D001761:Bleomycin