Bone morphogenetic protein-7 and connective tissue growth factor: novel targets for treatment of renal fibrosis?
Renal fibrosis is the major determinant in progression of kidney disease and results from an inappropriate response to acute and chronic kidney injury. Transforming growth factor (TGF)-beta1 is the driving force behind renal fibrosis and has since long been regarded as the key factor to be targeted in prevention and treatment of renal fibrosis. Despite the impressive results obtained in experimental renal fibrosis, TGF-beta1 blockade has not yet translated into an effective and safe therapeutic in human patients. Therefore, it remains important to explore the role of additional growth factors which are involved in renal regeneration and fibrosis. Recently, bone morphogenetic protein (BMP)-7 and connective tissue growth factor (CTGF) have both emerged as novel modulators of profibrotic TGF-beta1 activity. The expression of BMP-7 is decreased in various models of renal disease, while CTGF is strongly upregulated in experimental and human renal fibrosis. In experimental kidney injury, administration of BMP-7 or inhibition of CTGF have been sufficient to result in striking improvement of renal function and structure. This review summarizes the current knowledge of BMP-7 and CTGF in the kidney, and discusses their therapeutic potential in renal fibrosis.
Nguyen
Tri Q
TQ
Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Goldschmeding
Roel
R
D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000378:metabolism / Q000627:therapeutic use*; D055513:Connective Tissue Growth Factor; D005355:Fibrosis; D006801:Humans; D017874:Immediate-Early Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; C526317:CCN2 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor