Project/Area Number |
12671042
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Kidney internal medicine
|
Research Institution | Kyushu University |
Principal Investigator |
FUKUDA Kyoichi Kyushu Univ Hospital, Research associate, 医学部附属病院, 助手 (90294925)
|
Co-Investigator(Kenkyū-buntansha) |
KANAI Hidetoshi Kyushu Univ Hospital, Research associate, 医学部附属病院, 助手 (20311839)
HIRAKATA Hideki Kyushu Univ Hospital, Ass. Professor, 医学部附属病院, 助教授 (70181146)
|
Project Period (FY) |
2000 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
|
Keywords | podocyte / glomerulosclerosis / nephrotic syndrome / GLEPP1 / adriamycin nephropathy / cell cycle / dedifferentiation / GLEPP-1 / 増殖因子 / p21 |
Research Abstract |
1. Examination of renal biopsy samples in human idiopathic nephrotic syndrome Quantitative PCR showed that glomerular mRNA levels of podocyte specific protein, in particular GLEPP1, in nephrotic syndrome were lower than those in normal control. Of primary diseases, GLEPP1 mRNA levels in both focal segmental glomerulosclerosis (FSGS) and membranous nephropathy (MGN) were significantly lower than those in control, whereas GLEPP1 mRNA levels in minimal change disease (MCD) only tended to be lower than those in control. In addition, GLEPP1 mRNA levels in FSGS were significantly lower than those in MCD. Immunohistochemical staining showed that GLEPP1 protein expression decreased in order from MCD to MGN to FSGS as compared to that in normal. These data indicate glomerular GLEPP1 expression is down-regulated in patients with idiopathic nephrotic syndrome, suggesting a phenotypic change of podocyte. Furthermore, the quantification of GLEPP1 expression could be useful to differentiate FSGS from MCD. 2. Examination of a rat model of progressive glomerulosclerosis SD rats received two injections of adriamycin (ADR), and a subgroup of ADR rats received angiotensin II (AII) receptor blocker candesartan (ADR+CAN). Normal control rats were injected with saline (CON). Rats were sacrificed at week 4, 12, and 20. ADR rats showed progression of glomerulosclerosis and proteinuria. In immunohistochemical study, ADR rats showed high desmin expression (a marker of podocyte injury), and significant decrease in the number of WT1 positive podocyte. Immunostaining for synaptopodin was decreased, and de novo expression of both p21 and Ki67 were observed, which were negative on podocyte of CON rats. ADR+CAN showed signs of inhibition of glomerulosclerosis and resolution of proteinuria to the levels similar to CON. These data suggest ADR-induced FSGS is characterized by injury and dedifferentiation of podocytes and AII might play a major role in podocyte injury.
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