BMP-7 Does Not Protect against Bleomycin-Induced Lung or Skin Fibrosis |
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| Authors: | Lynne A Murray Tillie L Hackett Stephanie M Warner Furquan Shaheen Rochelle L Argentieri Paul Dudas Francis X Farrell Darryl A Knight |
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| Institution: | 1. Immunobiology Department, Tissue Remodeling and Metabolism Department, Centocor, Radnor, Pennsylvania, United States of America.; 2. James Hogg iCapture Centre for Cardiovascular and Pulmonary Research, St Paul''s Hospital, Vancouver, Canada.; 3. Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada.;University of Giessen Lung Center, Germany |
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| Abstract: | Bone morphogenic protein (BMP)-7 is a member of the BMP family which are structurally and functionally related, and part of the TGFβ super family of growth factors. BMP-7 has been reported to inhibit renal fibrosis and TGFβ1-induced epithelial-mesenchymal transition (EMT), in part through negative interactions with TGFβ1 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 TGFβ1-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 TGFβ1; and did not modulate TGFβ1 -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. |
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