Expression of osteogenic protein-1 mRNA in cultured kidney cells

Osteogenic protein-1 (OP-1 or BMP-7) is a multifunctional cytokine that regulates the development of several tissues during embryogenesis, including the skeleton, eye, and kidney. In postnatal life, OP-1 expression is most abundant in the kidney, although the cellular localization of this expression has not been described. In this study, we utilized a cell culture approach to localize OP-1 mRNA expression in various renal cell types and to determine potential target cells for OP-1 effects. OP-1 mRNA expression was demonstrated in several glomerular cell types, such as mesangial, epithelial, and endothelial cells. Distal tubule MDCK cells also expressed OP-1 mRNA but human proximal tubule HK-2 cells did not. Multiple OP-1 transcripts, which ranged in size from 1.6 to 3.8 kb, were observed in both glomerular and tubule cells. Interestingly, the pattern of expression varied among the different cell types, suggesting cell-specific expression of OP-1 mRNA. Analysis of OP-1 receptor expression revealed transcripts for BMP receptors type IA and IB in HK-2 cells and transcripts for BMPR-IA and ALK-2 in mesangial cells. Treatment of HK-2 cells with OP-1 (300 ng/ml) for 24-48 hr increased cellular proliferation whereas treatment of cells with transforming growth factor-beta had no effect. Mesangial cell proliferation was not affected by OP-1. The results suggest that OP-1 is produced in the renal glomerulus and then travels to the proximal tubule to regulate the proliferation of cells in this region of the nephron.