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Bone morphogenetic protein signaling is essential for correct vascularization of lungs and kidneys
Author(s) -
Yao Yucheng,
Jumabay Medet,
Wang Anthony,
Bostrom Kristina I
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.235.1
Subject(s) - bone morphogenetic protein , angiogenesis , bone morphogenetic protein receptor , matrix gla protein , kidney , bmpr2 , bone morphogenetic protein 2 , lung , genetically modified mouse , biology , microbiology and biotechnology , transgene , endocrinology , pathology , medicine , cancer research , kidney disease , biochemistry , hyperphosphatemia , gene , in vitro
Vascularization of growing organs is a highly coordinated process. Matrix Gla Protein (MGP) is expressed in lungs and kidneys during organ growth and inhibits bone morphogenetic protein (BMP)‐4 and ‐7, essential for both lung and kidney formation and angiogenesis. We hypothesized that BMP signaling is essential for correct organ vascularization. MGP deficient and MGP transgenic mice were used to study BMP signaling and vascularization in lungs and kidneys. Micro CT imaging showed a dramatic increase in vascular formation with evidence of abnormal arteriovenous connection in MGP deficient mice, whereas vascular growth was inhibited in MGP transgenic mice. Expression of activin‐like kinase receptor (ALK)1, ALK2, ALK5 and VEGF, known to be induced by BMP in endothelial cells, was significantly increased in MGP deficiency, but decreased when MGP was overexpressed. Unexpectedly, similar changes occurred in the type II epithelial lung cells and the mesenchymal kidney cells, suggesting that this system may coordinate vessel growth with the growth of organ‐specific elements. The levels of BMP‐4 and BMP‐7 did not significantly change, although BMP‐7 appeared to play a more important role in kidney vascularization. We conclude that timely inhibition of BMP‐4 and ‐7 by MGP in lungs and kidneys is essential for appropriate organ vascularization. Research support: NIH/NHLBI, AHA.