OSTEOGENIC PROTEIN-1 MESSENGER-RNA EXPRESSION IS SELECTIVELY MODULATED AFTER ACUTE ISCHEMIC RENAL INJURY

Osteogenic protein-1 (OP-1) is a morphogenetic factor highly expressed in the kidney and involved in tissue repair and development. Homozygo us OP-1-deficient mice die shortly after birth due mainly to arrest of renal growth and differentiation. Because postischemic injury involve s several repair mechanisms, this study examined whether kidney OP-1 m RNA expression is modulated after ischemia. Acute ischemic renal injur y was achieved in rats by unilateral clamping of the renal pedicle fol lowed by reperfusion. Rats were killed at 3, 6, 12, 24, and 48 h and 7 d after reperfusion, and kidneys were microdissected and analyzed by histology and Northern and Western blots. Changes in OP-1 mRNA were de termined by measuring the ratio of OP-1/glyceraldehyde 3-phosphate deh ydrogenase signals for each OP-1 transcript (4.0 and 2.4 kb) from isch emic, opposite, and sham-operated rats. The OP-1 mRNA content fur tran script 4.0 kb was fivefold lower in the whole ischemic kidney compared with that in sham animals 24 h after reperfusion. In the ischemic med ulla, OP-1 mRNA was strikingly downregulated 20-fold when compared wit h the ischemic cortex. Results for transcript 2.4 kb and for the other time points were comparable. OP-1 mRNA expression was also affected i n the opposite medulla compared with the sham medulla. However, only i n the ischemic medulla was the relative OP-1 content significantly low er at all time points. Similar results were obtained when analyzing OP -1 protein by Western blot at 24 h after reperfusion. Seven days after reperfusion, the levels of OP-1 mRNA returned to baseline. In conclus ion, kidney OP-1 mRNA and protein are selectively downregulated in the medulla after acute ischemic renal injury. OP-1 modulation may be a k ey element for kidney repair.