Osteogenic protein-1 (bone morphogenetic protein-7) reduces severity of injury after ischemic acute renal failure in rat
| Autor: | Mislav Jelić, Don Jin, Vanja Bašić, Nikolina Bašić, Susan Ryan, Haimanti Dorai, J. Maliakal, B. Dattatreyamurty, Ana Stavljenić, Alyssa A. Shepard, Dunja Rogić, Denise Griffiths, T. K. Sampath, Mei-Shu Shih, Slobodan Vukicevic, W. Jones, M. Pastorcic |
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| Rok vydání: | 1998 |
| Předmět: |
Male
medicine.medical_specialty Bone Morphogenetic Protein 7 Ischemia Kidney development Renal function Apoptosis Biology Kidney chemistry.chemical_compound Transforming Growth Factor beta Internal medicine medicine Animals Humans RNA Messenger Rats Wistar Growth Substances Blood urea nitrogen Creatinine Acute kidney injury General Medicine Acute Kidney Injury Intercellular Adhesion Molecule-1 medicine.disease Recombinant Proteins Rats Surgery Bone morphogenetic protein 7 medicine.anatomical_structure Endocrinology chemistry Bone Morphogenetic Proteins Research Article |
| Zdroj: | Journal of Clinical Investigation. 102:202-214 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci2237 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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