Cloning of the 5'-flanking region of the murine bone morphogenetic protein-7 gene.

BMP-7, a member of the bone morphogenetic protein subfamily of the TGFbeta-superfamily is highly expressed in the murine kidney. BMP-7 is involved in fetal nephron development and mesenchymal to epithelial cell differentiation. Constitutive BMP-7 expression is found in tubular and glomerular epithelial cells of the adult kidney. BMP-7 may play a role in physiology and pathophysiology of the adult kidney since BMP-7 gene expression in acute renal ischemia is diminished and injection of recombinant BMP-7 into rats with ischemic acute renal failure preserves renal function. In order to investigate the transcriptional regulation of BMP-7, this study was undertaken to clone and characterize the promoter of the murine BMP-7 gene. A 1394 bp sequence of the 5'-flanking region of the BMP-7 gene was isolated and subcloned. No TATA and CAAT box consensus motifs could be identified as shown for promoters of other BMPs. Using in vitro transfection assays, the 5'-flanking region revealed moderate to strong basal promoter activity. PMA increased basal BMP-7 promoter activity. Thus BMP-7 gene transcription might involve at least in part a PKC-dependent pathway. The cloning of a 5'-flanking region of the BMP-7 gene should provide a useful tool for future studies on the transcriptional regulation of BMP-7 gene expression.