engleski

Osteogenic protein-1 (Bone morphogenetic protein-7) protects against renal injury following ischemia in rats

Osteogenic protein-1 (OP-1/BMP-7), a member of TGF-B superfamily of proteins, is required for the kidney development and OP-1/BMP-7 null mutation mice die shortly after birth due to renal failure. In the present study, we examined the ability of systemically administered recombinant human OP-1 to modulate the degree of injury following ischemia and reperfusion in rats. Pharmacokinetic studies indicate that high serum levels of OP-1 were achieved after IV injection followed by a steadily decline with a halflife of about 30 minutes. Bioavailability studies show that 125-I-OP-1 specifically bound to plasma membrane fractions of the kidney and about 140 and 270 ng OP-1/g of tissue was available to the medulla or cortex, respectively, when 250 ug/kg bw of 125-I-OP-1 was injected. Evaluation of therapeutic effects indicate that OP-1 significantly suppresses blood urea nitrogen and serum creatinine levels and effectively increases the survival rate when applied within 16 hours after injury. Additional histochemical and molecular analyses demonstrate that OP-1: 1) improves renal hemodynamic properties as shown by increased glomerular filtration rate, 2) maintains the integrity of vascular smooth muscle cells in the S3 zone as qualified by expression of smooth muscle alpha-actin, 3) suppresses inflammation by downregulating the expression of intercellular adhesive molecule, I-CAM, in vascular endothelium, 4) minimizes infarction and cell necrosis, and 5) reduces programmed cell death during the recovery phase. These data collectively indicate that OP-1 averts damage associated with ischemia and reperfusion to kidney and, as such, may provide a basis for the treatment of acute renal failure.

OP-1 (BMP-7); renal injury

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