| Co-Investigator(Kenkyū-buntansha) |
TOYA Yoshiyuki Yokohama City University, YCU School of Medicine, Associate Professor, 附属病院, 準教授 (30237143)
HASHIMOTO Tatsuo Yokohama City University, YCU School of Medicine, Assistant Professor, 医学部, 助手 (20363806)
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| Research Abstract |
1. Regulatory roles of podocyte slit membrane associated molecules in cell polarity in diabetes nephropathy : Streptozotosin-induced diabetic mice.
Streptozotosin (STZ) (125 mg/kg BW) was injected twice. 12-weeks after the injection, both blood sugar and proteinuria were increased. Periodic Acid-Schiff (PAS) stained area was also increased. In angiotensin type I receptor gene-deficient mice, blood sugar, proteinuria, and PAS stained area were unchanged. Expressions of nephrin, CD2AP, ZO.1, PKCX, PAR3, PARE, and ASIP in renal cortex are now analyzing.
2. Regulatory roles of podocyte slit membrane associated molecules in diabetes nephropathy : db/db mice.
db/db mice exhibited severe albuminuria and increased PAS stained area at 6 months of age. In db/db/mice treated with angiotensin type I receptor blocker (ARB) from 3 to 6 months of age, albuminuria and increased PAS stained area were ameliorated. Increased expressions of nephrin, WT-1, podocin, and CD2AP in renal cortex of db/db mice were also ameliorated by ARB treatment. Expressions of regulatory factor for cell polarity, PKCλ, PKCζ, and ASIP, were unchanged. In db/db/mice, urinary excretion of 8-OHdG and isoprostan and glomerular expression of 8-OHdG were increased, and which were ameliorated by ARB treatment. Angiotensin II stimulates glomerular oxidative stress and increases proteinuria in diabetic nephropathy. Urinary excretion of 8-OHdG and isoprostan may indicate glomerular oxidative stress.
3. Podocyte specific PKCλ, gene-deficient mice
Podocyte specific PKCλ gene-deficient mice are under analysis.
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