2015 Fiscal Year Final Research Report
HGF-mediated functional supression of toll-like receptors in an innate immune system under ischemic diseases
Project/Area Number |
23590458
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Experimental pathology
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Research Institution | Osaka University |
Principal Investigator |
Mizuno Shinya 大阪大学, 医学(系)研究科(研究院), 助教 (10219644)
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Co-Investigator(Renkei-kenkyūsha) |
NAKAMURA TOSHIKAZU 大阪大学, 先端科学イノベーションセンター, 特任教授 (00049397)
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Project Period (FY) |
2011-04-28 – 2016-03-31
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Keywords | HGF / c-Met / 虚血性疾患 / トール様受容体 / マクロファージ / TLR4 / HMGB1 |
Outline of Final Research Achievements |
HGF improves pathological conditions during ischemic organ diseases through inducing anti-apoptotic and regenerative properties. There is now emerging evidence to show that over-activation of “innate immune system” by HMGB1 triggers excessive inflammatory events and accelerates organ dysfunction. Using a mouse model of renal ischemia, we demonstrated that HGF-mediated anti-apoptotic outcomes in parenchaymal cells leads to the suppression of extra-cellular HMGB1 secretion. Furthermore, we found that HGF directly targeted macrophages to intercept HMGB1-TLR4 signaling transduction, followed by the repression in NF-κB activations. Overall, we delineated the new functions of HGF, such as (i) inhibition of HMGB1-primed activation of TLR4 downstream (i.e., receptor side) and (ii) suppression of HMGB1 secretion from dying cells (i.e., ligand side) as well. Such a dual property of HGF likely contributes to the improvement in ischemic organ disorders.
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Free Research Field |
実験病理学
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