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

Autori
Vukičević, Slobodan ; Bašić, Vanja ; Rogić, Dunja ; Bašić, Nikolina ; Shih, Mei-Shu ; Shepard, Alyssa ; Jin, Don ; Dattatreyamurty, Bosukonda ; Jones, William ; Dorai, Haimanti ; Ryan, Susan ; Griffiths, Denise ; Maliakal, James ; Jelić, Mislav ; Pastorčić, Maria ; Stavljenić Rukavina, Ana ; Sampath, Kuber T.

Izvornik
Journal of Clinical Investigation (0021-9738) 102 (1998), 1; 202-214

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
osteogenic protein-1; acute renal failure; TGF-beta superfamily; idney repair and regeneration; ischemia and reperfusion; cytoprotection; suppression of inflammation; maintenance of vascular smooth muscle cells

Sažetak
We have shown tat osteogenic protein-1 (OP-1) is responsible for the induction of nephrogenic mesenchyme during kidney development. Gene knock-out studies showed that OP-1 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 treatement of acute renal failure after 60 min bilateral renal artery occlusion in rats. Bioacailability 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 than 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 preserved kidney function, as determined by reduced blood urea nitrogen and serum creatinine, and increased survival rate when administered 10 min before or 1 or 16h after ischemia, and then at 24-h intervals up to 72h 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 smoothe muscle cell phenotype in pericellular capillariess ; 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.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti, Farmacija

POVEZANOST RADA