2014 Fiscal Year Final Research Report
Study on the mechanism of free cholesterol metabolism of hepatic stellate cell in liver fibrosis
| Project/Area Number |
24790719
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Gastroenterology
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| Research Institution | Keio University |
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Principal Investigator |
|
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| Project Period (FY) |
2012-04-01 – 2015-03-31
|
| Keywords | 遊離コレステロール / 肝臓線維化 |
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| Outline of Final Research Achievements |
Given the growing number of metabolic syndrome patients in recent years, the incidence of nonalcoholic steatohepatitis increases in Japan. Accumulation of free cholesterol in hepatic stellate cell (HSC) increased levels of Toll-like receptor 4 (TLR4), leading to down-regulation of bone morphogenetic protein and activin membrane-bound inhibitor (a pseudoreceptor for transforming growth factor [TGF]β); the HSCs became sensitized to TGFβ-induced activation. Acyl-coenzyme A: cholesterol acyltransferase (ACAT) catalyzes the conversion of free cholesterol to cholesterol ester, which prevents excess accumulation of free cholesterol. ACAT1 deficiency exaggerates liver fibrosis mainly through enhanced free cholesterol accumulation in HSCs. Regulation of ACAT1 activities in HSCs could be a target for treatment of liver fibrosis.
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| Free Research Field |
消化器内科、肝臓病学
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