| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Research Abstract |
SIRPa is a transmembrane protein with tyrosine phosphorylation sites in its cytoplasmic region where two tyrosine phosphatases, SHP-1/SHP-2, bind to in a phosphorylation-dependent manner, and is expressed by podocytes. We examined the role of SIRPa in podocytes using knock-in mice expressing mutant SIRPa that lacks a cytoplasmic region. While there was no morphological abnormalities in the kidneys of the SIRPa-mutant mice on light microscopy, electron microscopic examination revealed abnormal podocytes with irregular major processes and wider and flattened foot processes in the SIRPa-mutant mice. Impaired renal functions and slight albuminuria were demonstrated in the mutant mice. In addition, adriamycin injection induced massive albuminuria along with focal glomerulosclerosis in the SIRPa-mutant mice, while their wild-type counterparts were resistant to adriamycin. These data indicate that SIRPa is involved in the regulation of podocyte structure and function as a filtration barrier.
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