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 |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Osaka University |
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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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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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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 / 自然免疫 / 肝細胞増殖因子 / TLR４ / HMGB１ / MHGB1 |
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| 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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Report
(6 results)
Research Products
(48 results)
