2004 Fiscal Year Final Research Report Summary
Basic research for the development of new therapeutic measures against progressive tubuloinetsrtitial injury.
| Project/Area Number |
15390269
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Nagoya University |
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Principal Investigator |
MATSUO Seiichi Nagoya University, Graduate School of Medicine, professor, 大学院・医学系研究科, 教授 (70190410)
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| Co-Investigator(Kenkyū-buntansha) |
YUZAWA Yukio Nagoya University, Graduate School of Medicine, Assistant professor, 大学院・医学系研究科, 講師 (00191479)
MORITA Yoshiki Nagoya University, University Hospital, Research Associate, 医学部附属病院, 助手 (10335044)
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| Project Period (FY) |
2003 – 2004
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| Keywords | progressive renal injury / Tubulointerstitial Injury / Proteinuria / Complement / Novel Therapy / Renal Protection / Cellular Infiltration / Renal Fibrosis |
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| Research Abstract |
(1)Urinary MAC excretion was studied in 140 patients with proteinuria and followed up for 40 months. Multi-factorial analysis revealed that the increased urinary MAC excretion was an independent risk factor for progression of renal injury.
(2)Brush border vesicles(BBVs) isolated from human proximal tubular epithelial cells were analyzed by SDS-PAGE and transfer membrane. BBVs activated complement and the fraction binding C3b was further analyzed. It was shown that complement was activated by BBVs and there were fragments to bind C3b. The further analysis is necessary to characterize complement activating substances in BBVs.
(3)One of the main mechanisms of progressive tubulointerstitial injury is the infiltration of macrophages/monocytes. The strategy to iniibit macrophage infiltration was tested by using in vivo gene transfer. The effectiveness of this newly developed method was proven in a rat model of protein overlaod nephropathy.
(4)The target molecules existing in the proximal tubular cells including midkine(MK), toll like receptors, and caveolin were analyzed. All of these molecules were proven to be a target to manipulate progression og the progressive renal injury in vivo and in vitro.
(5)In particularly, MK, a novel heparin-binding growth factor, is increased in its expression during renal injury, and the extent of tubulointerstitial injury was significantly lessened in MK knock out mice. Furthermore, inhibition of MK expression by antisense-ODN in the proximal tubules significantly reduced renal injury in vivo.
(6)All of the above observation obtained by the present research project revealed that several mechanismas/molecules were involved in the progression of renal injury, and for the clinical use, we must overcome the hurdles concerning efficacy, specificity, economy, and durability.
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Research Products
(12 results)
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[Journal Article] A srine/threonine kinase, Cot/Tpl2, modulates bacterial DNA-induced IL12 production and helper T cell differentiation.2004
Author(s)
Sugimoto K, Ohata M, Miyoshi J, H.I, Tsuboi N, Masuda A, Yoshikai Y, Takamoto M, Sugane K, Matsuo S, Shimada Y, Matsuguchi T
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Journal Title
Journal of Clinical Investigation 114
Pages: 857-866
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Anti-monocyte chemoattravtant protein-1 gene therapy attenuates renal injury induced by protein overload proteinuria.2003
Author(s)
Shimizu H, Maruyama S, Yuzawa Y, Kato T, Miki Y, Suzuki S, Sato W, Morita Y, Maruyama H, Egashira K, Matsuo S
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Journal Title
Journal of American Society of Nephrology 14
Pages: 1496-1505
Description
「研究成果報告書概要(欧文)」より
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