Bone morphogenetic protein-7 (BMP7) in chronic kidney disease.
Bone morphogenetic protein-7 (BMP7) is a member of the BMP-subfamily of perhaps a dozen proteins within the TGFbeta-superfamily of cysteine-knot fold cytokine-growth factors. BMP7 has pivotal functions during renal and eye development. In adult organisms, BMP7 is heavily expressed in kidney, specifically in podocytes, distal tubules and collecting ducts. The activity of BMP7 is reduced by inhibitors including some members of the dan-cerberus group and CTGF but can be enhanced by endoglin and KCP. Renal BMP7 disappears early in fibrogenic renal diseases which may facilitate progression. Exogenous administration of rhBMP7 or transgenic overexpression reduces renal fibrogenesis and apoptosis as well as transdifferentiation of epithelial cells. BMP7 improves maintenance of nephron function and structural integrity. These antifibrogenic activities result from inhibition of the nuclear translocation of TGFbeta-activated smad3 by smad6 downstream of BMP7-activated smad5. Although at present the beneficial effects of BMP7 have only been studied in rodent models of chronic renal diseases, there is promise for therapeutic utility of rhBMP7 or small molecule BMP7 agonists in patients.
Mitu
Grace
G
Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center and UCLA, Torrance, CA 90502, USA.
Hirschberg
Raimund
R
D055398:Bone Morphogenetic Protein 3; D055419:Bone Morphogenetic Protein 7; D052004:Bone Morphogenetic Protein Receptors / Q000037:antagonists & inhibitors / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000819:agonists / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D002908:Chronic Disease; D003928:Diabetic Nephropathies / Q000235:genetics*; D005340:Fibrinogen / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005786:Gene Expression Regulation; D006801:Humans; D007265:Inhibins / Q000502:physiology; D007668:Kidney / Q000502:physiology / Q000503:physiopathology; D007674:Kidney Diseases / Q000235:genetics*; D051437:Renal Insufficiency / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000819:agonists / Q000187:drug effects / Q000235:genetics*
C525757:BMP3 protein, human; C525819:BMP7 protein, human; D055398:Bone Morphogenetic Protein 3; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta; D007265:Inhibins; D005340:Fibrinogen; D052004:Bone Morphogenetic Protein Receptors