engleski

The role of BMPs in kidney repair

Several bone morphogenetic proteins, including BMP-2 to -7 are expressed in developing and adult kidney. OP-1 (BMP-7) is capable of inducing metanephric mesenchyme differentiation during kidney development and gene knock-out studies showed that OP-1 null mutations mice die shortly after birth due to renal failure, although induction of metanephric structures in null mutations mice initially occurred (E11-E13). To further investigate the placental transfer of OP-1 during different stages of development we have studied the distribution of 125I-OP- injected in teil vein of pregnant mice. We found that 125I-OP-1 passes the placenta and localizes in developing fetal organs, in particular kidneys, up to day 14 of gestation. At later pregnancy, between day 14 and 18, 125I-OP OP-1 did not pass the placenta and entered fetal blood vessels. Therefore, circulating OP-1 in heterozygous mothers might induce fetal nephrogenesis and mask the developmental role of OP-1. The intensity of expression of BMP-2 to -7 changes during development and in post natal life, with BMP-4, BMP-6 and OP-1 being present at all investigated time periods (E12 to 1.5 years). OP-1 has a profound protective effect on kidney function in acute renal failure. In both rat models of ischemic and nephrotoxic renal injury OP-1 preserved kidney function and increased survival rate when administered at 10 min before or 1 and 16 h after injury. Additional analyses demonstrate that OP-1: minimizes infarction and cell necrosis, suppresses inflammation, maintains the vascular smooth muscle cell integrity of pericellular capillaries, and reduces apoptosis in rats with acute renal failure. These data suggest that OP-1 prevents the loss of kidney function and stimulates repair of damaged nephrons and may, therefore, provide a basis for the treatment of acute renal failure. The research of the role of other BMPs during development and in adult kidney is ongoing. Vukicevic S et al.: Proc Natl Acad Sci USA 93:9021, 1996. Vukicevic S et al: J Clin Invest 102:202, 1998.

bone morphogenetic proteins; kidney

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