| Budget Amount *help |
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1996: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
Heat shock proteins (HSPs) are rapidly synthesized in cells in response to a varicty of stresses. These proteins are highly conserved through evolution. Recently, we have purified mammalian HSP60, HSP73, and HSP90, and produced specific antibodies against these HSPs. We previously reported the induction and altered localization of HSP73 and HSP90 in animal models for drug-mediated acute renal failure. In the present report, we have examined further the induction and altered localization of HSPs in other animal models for acute renal injury and in human diseased kidneys.
1 : In rat kidneys after transient ischemia, both HSP73 and HSP90 were induced in the cytoplasm of injured and regenerative epithelial cells of proximal tubules. Serial immunoblot analysis of renal extracts revealed the biphasic induction of HSP73 and HSP90 during the degenerative and regenerative phases after ischemia. These results may indicate that HSPs have important roles in the protection and repair of target cells
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from renal ischemia.
2 : In rat kidneys with gentamicin-induced acute tubular injury, immunohistochemiocal studies at light microscopic level showed that HSP73 appcaredto be induced and accumulated in the lysosomes of damaged epithelial cells of proximal tubules. We have confirmed this using electron microscopic immunohistochemistry. HSP73 may have a role in the disposition of damaged proteins for repair of target cells from gentamicin nephropathy.
3 : In normal rat kidneys, HSP60 was localized within the cytoplasm and the mitochondria in tubular epithelial cells. In addition, HSP60 was expressed at the luminal side of tubular epithelial cells between the Henle's loops and collecting ducts. After water-restriction, the induction of HSP60 at the luminal side of tubular epithelial cells was greater than that observed in normal kidneys. On immunoblot analysis of renal papilla extracts, increased amounts of HSP60 were found in association with water-restriction. These results suggest that HSP60 may play a role in water reabsorption.
4.In human diseased kidneys, both HSP73 and HSP90 were induced in the cellular crescent of the glomeruli and regenerative tubular cells. These results suggest that HSPs have important roles both in the formation of cellular crescents and in the repair of injured cells. Less
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