Molecular mechanisms of multiple organ dysfunction in pancreatitis with infection
| Project/Area Number |
17591606
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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 |
Anesthesiology/Resuscitation studies
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| Research Institution | University of Toyama (2006)
Hokkaido University (2005) |
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Principal Investigator |
MATSUDA Naoyuki University of Toyama, Department of Molecular Medical Pharmacology, Associate Professor, 大学院医学薬学研究部, 准教授 (50332466)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | Toll-like receptor / THE receptor / NF-κB / AP-1 / PAR2 / gene therapy / 急性膵炎 / NF-kB / activator protein-1 |
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| Research Abstract |
This research revealed that the acute pancreatitis mouse using cerulein up-regulated protease activated receptor 2 (PAR2) in the various main internal organs including lung, atrium and kidney. By a process of repeated subcutaneous administration of cerulein, expression of PAR2 elevated at transcriptional and protein levels in the main organs. The intercellular signaling via PAR2 lead to activation of transcription factor NF-κB and AP-1, by which inflammatory receptors such as Toll-like receptor 2 (TLR2), TLR4, TLR9 and TNF-receptor 1 were up-regulated at transcriptional levels. Inhibition of transcription factor NF-κB and AP-1 by their decoy oligonucleotides can reduce the overexpression of inflammatory receptors and production of inflammatory molecules such as iNOS, COX2 and ICAM1 by the stimulation of ligands of TLR in the lung, atrium and kidney of pancreatitis. It was thought that gene therapy of transcription factor NF-κB and AP-1 is an effective therapy for the reduction of enhanced intensity of inflammation in the main organs of acute pancreatitis with 2^<nd> attack of infection.
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Report
(3 results)
Research Products
(3 results)
