Expression of bone morphogenetic protein-7 mRNA in normal and ischemic adult rat kidney

BMP-7, a member of the bone morphogenic protein subfamily (BMPs) of the tra nsforming growth factor-beta superfamily of secreted growth factors, is abu ndantly expressed in the fetal kidney. The precise role of this protein in renal physiology or pathology is unknown. A cDNA that encodes rat BMP-7 was cloned and used as a probe to localize BMP-7 mRNA expression by in situ hy bridization in the adult rat kidney. The highest expression of BMP-7 mRNA c ould be seen in tubules of the outer medulla. In glomeruli, a few cells, ma inly located at the periphery of the glomerular tuft, showed specific and s trong signals. Also, high BMP-7 mRNA expression could be localized to the a dventitia of renal arteries, as well as to the epithelial cell layer of the renal pelvis and the ureter. Preliminary evidence suggests that BMP-7 enha nces recovery when infused into rats with ischemia-induced acute renal fail ure. We examined BMP-7 mRNA expression in kidneys with acute renal failure induced by unilateral renal artery clamping. BMP-7 mRNA abundance as analyz ed by solution hybridization was reduced in ischemic kidneys after 6 and 16 h of reperfusion compared with the contralateral kidney. In situ hybridiza tion in ischemic kidneys showed a marked decrease of BMP-7 mRNA in the oute r medulla and in glomeruli. Utilizing rat metanephric mesenchymal cells in culture, we also demonstrate that BMP-7 induces epithelial cell differentia tion. Taken together, these data suggest that BMP-7 is important in both st imulating and maintaining a healthy differentiated epithelial cell phenotyp e.