2006 Fiscal Year Final Research Report Summary
Studies on the Pathogenesis and the Modulation of Kidney Diseases in Hypoxic Milieu
| Project/Area Number |
17590487
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory medicine
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| Research Institution | University of Fukui |
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Principal Investigator |
YOSHIDA Haruyoshi University of Fukui, Faculty of Medical Sciences, Professor, 医学部, 教授 (80135574)
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| Co-Investigator(Kenkyū-buntansha) |
KIMURA Hideki University of Fukui, Faculty of Medical Sciences, Associate Professor, 医学部, 助教授 (20283187)
TAKAHASHI Naoki University of Fukui Hospital, Assistant Professor, Assistant Professor, 医学部附属病院, 助手 (30377460)
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| Project Period (FY) |
2005 – 2006
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| Keywords | ischemic hypoxia / progressive kidney diseases / hypobaric hypoxic / milieu / cDNA array / PAI-1 / VEGF / MCP-1 / renal tubular cells |
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| Research Abstract |
(1) Pathological study on the progressive kidney Diseases :
We morphologically studied on the renal biopsy samples from the two representative progressive kidney diseases ; diabetic nephropathy and hypertensive nephrosclerosis. The results have shown that degree of renal dysfunction was strongly correlated with the severity of tubulointerstitial changes. In the progression of the tubulointerstitial changes, ischemic hypoxia induced by the reduced kidney perfusion was suggested as the major causative factor.
(2) Hypoxic response of cultured human proximal renal tubulat cells :
Because the proximal tubule is the major component in the tubulointerstitium, we performed in vitro culture experiments on human proximal renal tubular cell, under hypoxic condition (1% O2), and analyzed the production of various cytokines and chemokines. The cDNA array analysis has shown that hypoxia induced prominent mRNA induction of PAI-1 and VEGF. The further addition of inflammatory stimulation of TNF α, showed synergistic response of PAI-1 production, whereas such effect was not induced on the VEGF production. In chemokine analysis, there were significant decreases of MCP-1, osteopontin, and IP-10 in hypoxia condition.
(3) Pathological study on the kidney disease on mice bred in hypobaric hypoxic condition :
The mice were bred in a hypobaric hypoxic chamber for 72 hours, and the kidneys were immunopathologically examined. As a result, severe proliferative and swelling response of proximal tubular cells were observed. Pimonidazole staining which detects tissue hypoxia was significantly positive in the cortex area. Immunostainings on PAI-1, VEGF and PCP-1 were positively observed in the same area.
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