The role of Gab1 adaptor protein during stem /progenitor cell-mediated liver regeneration in acute liver failure
Project/Area Number |
15K08997
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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 |
Gastroenterology
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Research Institution | Osaka University |
Principal Investigator |
KISO SHINICHI 大阪大学, 医学系研究科, 特任准教授 (40335352)
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Co-Investigator(Kenkyū-buntansha) |
吉田 雄一 大阪大学, 医学系研究科, 特任助教 (30457014)
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Project Period (FY) |
2015-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | Gab1 / 重症肝不全 / 肝再生 / 幹細胞 / 肝幹/前駆細胞 |
Outline of Final Research Achievements |
In this study, we assessed the role of Gab1 in stem/progenitor cell-mediated liver regeneration using chemically induced model. To induce the adult hepatic stem/progenitor cells, the wild type (WT) and hepatocyte specific Gab1 conditional knockout (CKO) mice were treated with 0.1% of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet for 2-6 weeks. Liver to body weight ratio of CKO mice was significantly lower than that of WT mice at 2, 4 and 6 week after DDC exposure. CKO mice also had a significant higher mortality compared to WT mice due to severe cholestasis. The induction of the CK19 positive adult hepatic stem/progenitor cells was reduced in CKO livers compared with WT livers. Consistently, the gene expression of hepatic stem cell markers, such as EpCAM and CD133/Prominin1 was significantly reduced in CKO livers compared with WT livers. These data showed that Gab1 might play a crucial role in stem/progenitor cell-mediated liver regeneration.
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Report
(4 results)
Research Products
(26 results)
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[Journal Article] Increased expression of Forkhead box M1 transcription factor is associated with clinicopathological features and confers a poor prognosis in human hepatocellular carcinoma.2017
Author(s)
Egawa M, Yoshida Y, Ogura S, Kurahashi T, Kizu T, Furuta K, Kamada Y, Chatani N, Hamano M, Kiso S, Hikita H, Tatsumi T, Eguchi H, Nagano H, Doki Y, Mori M, Takehara T
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Journal Title
Hepatol Res.
Volume: 印刷中
Issue: 11
Pages: 1196-1205
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Ultra-deep sequencing analysis of resistance-associated variants during retreatment with simeprevir-based triple therapy after failure of telaprevir-based triple therapy in patients with genotype 1 hepatitis C virus infection.2017
Author(s)
Morishita N, Hiramatsu N, Oze T, Urabe A, Tahata Y, Yamada R, Yakushijin T, Hosui A, Iio S, Yamada A, Hagiwara H, Mita E, Yamada Y, Ito T, Inada M, Katayama K, Yabuuchi I, Imai Y, Hikita H, Sakamori R, Yoshida Y, Tatsumi T, Hayashi N, Takehara T.
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Journal Title
Hepatol Res.
Volume: 印刷中
Issue: 8
Pages: 773-782
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Hepatic aberrant glycosylation by N-acetylglucosaminyltransferase V accelerates HDL assembly.2016
Author(s)
Kamada Y, Kida S, Hirano KI, Yamaguchi S, Suzuki A, Hashimoto C, Kimura A, Sato M, Fujii H, Sobajima T, Yamamoto A, Ebisutani Y, Takamatsu S, Shinzaki S, Yoshida Y, Yamada M, Nagasaka H, Takehara T, Miyoshi E.
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Journal Title
Am J Physiol Gastrointest Liver Physiol.
Volume: 311
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Gab1 adaptor protein acts as a gatekeeper to balance hepatocyte death and proliferation during acetaminophen-induced liver injury in mice.2016
Author(s)
Furuta K, Yoshida Y, Ogura S, Kurahashi T, Kizu T, Maeda S, Egawa M, Chatani N, Nishida K, Nakaoka Y, Kiso S, Kamada Y, Takehara T.
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Journal Title
Hepatology
Volume: 63
Issue: 4
Pages: 1340-1355
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] The impact of an inosine triphosphate pyrophosphatase genotype on bilirubin increase in chronic hepatitis C patients treated with simeprevir, pegylated interferon plus ribavirin.2016
Author(s)
Tahata Y, Hiramatsu N, Oze T, Morishita N, Harada N, Yamada R, Yakushijin T, Mita E, Hagiwara H, Yamada Y, Ito T, Hijioka T, Inada M, Katayama K, Tamura S, Yoshihara H, Inoue A, Imai Y, Irishio K, Kato M, Hikita H, Sakamori R, Miyagi T, Yoshida Y, Tatsumi T, Hamasaki T, Hayashi N, Takehara T
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Journal Title
J Gastroenterol.
Volume: 51
Pages: 252-259
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Ectopic expression of N-acetylglucosaminyltransferase V accelerates hepatic triglyceride synthesis.2016
Author(s)
Kamada Y, Ebisutani Y, Kida S, Mizutani K, Akita M, Yamamoto A, Fujii H, Sobajima T, Terao N, Takamatsu S, Yoshida Y, Takehara T, Miyoshi E
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Journal Title
Hepatol Res.
Volume: 46
Issue: 3
Pages: 1189-129
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] A novel noninvasive diagnostic method for nonalcoholic steatohepatitis using two glycobiomarkers.2015
Author(s)
Kamada Y, Ono M, Hyogo H, Fujii H, Sumida Y, Mori K, Tanaka S, Yamada M, Akita M, Mizutani K, Fujii H, Yamamoto A, Takamatsu S, Yoshida Y, Itoh Y, Kawada N, Chayama K, Saibara T, Takehara T, Miyoshi E
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Journal Title
Hepatology.
Volume: 62
Issue: 5
Pages: 1433-1443
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Fetuin-A negatively correlates with liver and vascular fibrosis in nonalcoholic fatty liver disease subjects.2015
Author(s)
Kamada Y*, Sato M* (equally contributed), Takeda Y, Kida S, Ohara Y, Fujii H, Akita M, Mizutani K, Yoshida Y, Yamada M, Hougaku H, Takehara T, Miyoshi E.
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Journal Title
Liver Int
Volume: 35
Issue: 3
Pages: 925-35
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Presentation] Metabolic regulation of FoxM1 transcription factor by mevalonate-Rho pathways in human hepatocarcinoma.2016
Author(s)
Satoshi Ogura, Yuichi Yoshida, Tomohide Kurahashi, Mayumi Egawa, Kunimaro Furuta, Shinichi Kiso, Yoshihiro Kamada, Hayato Hikita, Tomohide Tatsumi and Tetsuo Takehara.
Organizer
The Liver Meeting 2016 - AASLD
Place of Presentation
HYNES CONVENTION CENTER, BOSTON, MA, USA
Year and Date
2016-11-11
Related Report
Int'l Joint Research
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[Presentation] Hepatic overexpression of oncogenic FoxM1 transcription factor promotes hepatocyte death and hepatic inflammation in mice.2016
Author(s)
Tomohide Kurahashi, Yuichi Yoshida, Satoshi Ogura, Mayumi Egawa, Kunimaro Furuta, Yoshihiro Kamada, Shinichi Kiso, Hayato Hikita, Tomohide Tatsumi, Tetsuo Takehara.
Organizer
The Liver Meeting 2016 - AASLD
Place of Presentation
HYNES CONVENTION CENTER, BOSTON, MA, USA
Year and Date
2016-11-11
Related Report
Int'l Joint Research
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[Presentation] A novel noninvasive diagnostic method for nonalcoholic steatohepatitis (NASH) using two glycobiomarkers2015
Author(s)
Yoshihiro Kamada, Masafumi Ono, Hideyuki Hyogo, Hideki Fujii, Yoshio Sumida, Kohjiroh Mori, Saiyu Tanaka, Makoto Yamada, Maaya Akita, Kayo Mizutani, Hironobu Fujii, Akiko Yamamoto, Shinji Takamatsu, Yuichi Yoshida, Yoshito Itoh, Norifumi Kawada, Kazuaki Chayama, Toshiji Saibara, Tetsuo Takehara, Eiji Miyoshi
Organizer
第66回米国肝臓学会議
Place of Presentation
Moscone Convention Center, San Francisco, USA
Year and Date
2015-11-17
Related Report
Int'l Joint Research
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