2013 Fiscal Year Final Research Report
Metabolic Analysis of the Cultured Hepatic Cell Persistently Infected with Hepatitis C Virus
| Project/Area Number |
23590551
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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 |
Virology
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| Research Institution | Keio University |
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Principal Investigator |
SUGIYAMA Kazuo 慶應義塾大学, 医学部, 特任准教授 (10242520)
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| Co-Investigator(Renkei-kenkyūsha) |
SAITO Hidetsugu 慶應義塾大学, 薬学部, 教授 (80186949)
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| Project Period (FY) |
2011 – 2013
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| Keywords | C型肝炎ウイルス / ペントースリン酸経路 / コレステロール / 脂肪酸 / Nrf2 / メタボローム / 脂肪滴 |
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| Research Abstract |
In this study, to explore the mechanism for metabolic alteration by hepatisis C virus (HCV), we established a hepatic cell line, HPI cell, persistently infected with HCV. This cell line accumulated massive lipid droplets showing prominent steatosis. Thus we performed integrated analysis by combining microarray and metabolomics. As a result, enhanced production of cholesterol and fatty acids by up-regulation of the rate limiting enzymes. Pentose phosphate pathway was enhanced with production of NADPH. Moreover, TCA cycle was also enhanced indicating hypermetabolic status of the HPI cell. It was speculated that constitutively activated Nrf2, which is a key transcription factor for metabolism, was attributed to the hypermetabolism of HPI cell.
In conclusion, HPI cell is a useful tool for research of not only HCV but also liver metabolism.
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Research Products
(15 results)
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[Journal Article] Prominent Steatosis with Hypermetabolism of the Cell Line Permissive for Years of Infection with Hepatitis C Virus2014
Author(s)
Sugiyama K, Ebinuma H, Nakamoto N, Sakasegawa N, Murakami Y, Chu P, Usui S, Ishibashi Y, Wakayama Y, Taniki N, Murata H, Saito Y, Fukasawa M, Saito K, Yamagishi Y, Wakita T, Takaku H, Hibi T, Saito H, Kanai T
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Journal Title
DOI
Peer Reviewed
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[Journal Article] Free cholesterol accumulation in hepatic stellate cells : Mechanism of liver fibrosis aggravation in nonalcoholic steatohepatitis in mice2014
Author(s)
Tomita K, Teratani T, Suzuki T, Shimizu M, Sato H, Narimatsu K, Okada Y, Kurihara C, Irie R, Yokoyama H, Shimamura K, Usui S, Ebinuma H, Saito H, Watanabe C, Komoto S, Kawaguchi A, Nagao S, Sugiyama K, Hokari R, Kanai T, Miura S, Hibi T
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Journal Title
Hepatology
Volume: 59(1)
Pages: 154-69
DOI
Peer Reviewed
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[Journal Article] p53/p66Shc-mediated signaling contributes to the progression of non-alcoholic steatohepatitis in humans and mice2012
Author(s)
Tomita K, Teratani T, Suzuki T, Oshikawa T, Yokoyama H, Shimamura K, Nishiyama K, Mataki N, Irie R, Minamino T, Okada Y, Kurihara C, Ebinuma H, Saito H, Shimizu I, Yoshida Y, Hokari R, Sugiyama K, Hatsuse K, Yamamoto J, Kanai T, Miura S, Hibi T
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Journal Title
J Hepatol
Volume: 57
Pages: 837-843
DOI
Peer Reviewed
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[Journal Article] A high-cholesterol diet exacerbates liver fibrosis in mice via accumulation of free cholesterol in hepatic stellate cells2012
Author(s)
Teratani T, Tomita K, Suzuki T, Oshikawa T, Yokoyama H, Shimamura K, Tominaga S, Hiroi S, Irie R, Okada Y, Kurihara C, Ebinuma H, Saito H, Hokari R, Sugiyama K, Kanai T, Miura S, Hibi T
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Journal Title
Gastroenterology
Volume: 142
Pages: 152-164
DOI
Peer Reviewed
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[Presentation] Usefulness of A Long-term (Over 2 years) Cultured Cell Clone Persistently and Productively Infected with HCV2012
Author(s)
Sugiyama K, Saito H, Sakasegawa N, Murakami Y, Ebinuma H, Nakamoto N, Usui S, Ishibashi Y, Chu P, Wakayama Y, Saito Y, Kanai T, Hibi T
Organizer
The 63rd Annual Meeting of the American Association for the Study of Liver Diseases
Place of Presentation
Boston, USA
Year and Date
20121109-13
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[Presentation] New Insights on Hepatic Inflammatory Pseudotumor by Gd-EOB-DTPA MR Imaging2012
Author(s)
Usui S, Chu P, Wakayama Y, Ishibashi Y, Nakamoto N, Yamagishi Y, Masugi Y, Ebinuma H, Sugiyama K, Tanimoto A, Kanai T, Saito H, Hibi T
Organizer
ACG 2012 Annual Scientific Meeting
Place of Presentation
Las Vegas, USA
Year and Date
20121019-24
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[Presentation] Age and the liver stiffness measured by Fibroscan are significant predictive values for hepatoma development in chronic liver diseases2011
Author(s)
Ishibashi Y, Ebinuma H, Sugiyama K, Nakamoto N, Yamagishi Y, Usui S, Cho HS, Umeda R, Wakayama Y, Takaishi H, Kanai T, Sakamoto M, Saito H, Hibi T
Organizer
62nd Annual Meeting of the American Association for the Study of Liver Diseases
Place of Presentation
San Francisco, USA
Year and Date
20111104-08
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[Presentation] Significant and continuous elevation of serum total cholesterol levels in patients with chronic hepatitis C who achieved sustained virological response by peginterferon and rivabirin treatment2011
Author(s)
Ebinuma H, Saito H, Sugiyama K, Nakamoto N, Yamagishi Y, Usui S, Cho HS, Umeda R, Ishibashi Y, Wakayama Y, Kanai T, Hibi T
Organizer
62nd Annual Meeting of the American Association for the Study of Liver Diseases
Place of Presentation
San Francisco, USA
Year and Date
20111104-08
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