Osteogenic protein-1 (bone morphogenetic protein-7) reduces severity of injury after ischemic acute renal failure in rat.

S Vukicevic; V Basic; D Rogic; N Basic; M S Shih; A Shepard; D Jin; B Dattatreyamurty; W Jones; H Dorai; S Ryan; D Griffiths; J Maliakal; M Jelic; M Pastorcic; A Stavljenic; T K Sampath

doi:10.1172/JCI2237

Osteogenic protein-1 (bone morphogenetic protein-7) reduces severity of injury after ischemic acute renal failure in rat.

S Vukicevic, V Basic, D Rogic, N Basic, M S Shih, A Shepard, D Jin, B Dattatreyamurty, W Jones, H Dorai, S Ryan, D Griffiths, J Maliakal, M Jelic, M Pastorcic, A Stavljenic, and T K Sampath

Published July 1, 1998 - More info

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Abstract

We have shown that osteogenic protein-1 (OP-1) (bone morphogenetic protein-7) is responsible for the induction of nephrogenic mesenchyme during embryonic kidney development. Gene knock-out studies showed that OP-1 null mutant mice die of renal failure within the first day of postnatal life. In the present study, we evaluated the effect of recombinant human OP-1 for the treatment of acute renal failure after 60 min bilateral renal artery occlusion in rats. Bioavailability studies in normal rats indicate that approximately 1.4 microg OP-1/ml is available in the circulation 1 min after intravenous administration of 250 microg/kg, which then declines steadily with a half life of 30 min. About 0.5% of the administered OP-1 dose/g tissue is targeted for OP-1 receptors in the kidney. We show that OP-1 preserves kidney function, as determined by reduced blood urea nitrogen and serum creatinine, and increased survival rate when administered 10 min before or 1 or 16 h after ischemia, and then at 24-h intervals up to 72 h after reperfusion. Histochemical and molecular analyses demonstrate that OP-1: (a) minimizes infarction and cell necrosis, and decreases the number of plugged tubules; (b) suppresses inflammation by downregulating the expression of intercellular adhesive molecule, and prevents the accumulation and activity of neutrophils; (c) maintains the expression of the vascular smooth muscle cell phenotype in pericellular capillaries; and (d) reduces programmed cell death during the recovery. Collectively, these data suggest that OP-1 prevents the loss of kidney function associated with ischemic injury and may provide a basis for the treatment of acute renal failure.

Osteogenic protein-1 (bone morphogenetic protein-7) reduces severity of injury after ischemic acute renal failure in rat.

S Vukicevic, V Basic, D Rogic, N Basic, M S Shih, A Shepard, D Jin, B Dattatreyamurty, W Jones, H Dorai, S Ryan, D Griffiths, J Maliakal, M Jelic, M Pastorcic, A Stavljenic, and T K Sampath

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Osteogenic protein-1 (bone morphogenetic protein-7) reduces severity of injury after ischemic acute renal failure in rat.

S Vukicevic, V Basic, D Rogic, N Basic, M S Shih, A Shepard, D Jin, B Dattatreyamurty, W Jones, H Dorai, S Ryan, D Griffiths, J Maliakal, M Jelic, M Pastorcic, A Stavljenic, and T K Sampath

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