Establishment of new treatment targeting lifestyle diseases and coagulation fibrinolytic system related to the development of NASH
Project/Area Number |
26461018
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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 | Nara Medical University |
Principal Investigator |
Noguchi Ryuichi 奈良県立医科大学, 医学部附属病院, 研究員 (30423908)
|
Co-Investigator(Kenkyū-buntansha) |
吉治 仁志 奈良県立医科大学, 医学部, 教授 (40336855)
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Co-Investigator(Renkei-kenkyūsha) |
MATSUMOTO MASANORI 奈良県立医科大学, 医学部, 教授 (60316081)
NAMISAKI TADASHI 奈良県立医科大学, 医学部, 講師 (20526850)
MORIYA KEI 奈良県立医科大学, 医学部, 講師 (40526852)
KITADE MITSUTERU 奈良県立医科大学, 医学部, 助教 (40526795)
MASHITANI TSUYOSHI 奈良県立医科大学, 医学部, 助教 (20401929)
|
Research Collaborator |
NISHIMURA NORIHISA
|
Project Period (FY) |
2014-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | NASH / 生活習慣病 / ARB / DPP-Ⅳ阻害剤 / SGLT-2阻害剤 / PAI-1阻害剤 / DPP4阻害剤 / PAI-1 / 肝線維化 / 非アルコール性脂肪肝炎 / DPPIV阻害剤 / DPPⅣ阻害剤 / 血管新生 |
Outline of Final Research Achievements |
In the rat NASH model, ARB and DPP-IV inhibitor innhibited liver fibrosis along with suppression of activated hepatic stellate cells (Ac-HSCs) and TGF-β expression, and treatment with both drugs further suppressed significantly as compared with either single agent. SGLT-2 inhibitor, which is a drug for treating diabetes mellitus, indirectly suppressed liver fibrosis through the insulin resistance-improving effect. PAI-1 inhibitor markedly inhibited the development of liver fibrosis along with suppression of Ac-HSC. Our in vitro data showed that PAI-I inhibitor directly suppressed proliferation of Ac-HSCs, expression of TGF-β mRNA and α1 collagen mRNA. Furthermore, clinical studies suggested the possibility of DPP-IV inhibitor for treating fatty liver disease with type 2 diabetes.
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] DNA methylation of angiotensin II receptor gene in nonalcoholic steatohepatitis-related liver fibrosis.2016
Author(s)
Asada K, Aihara Y, Takaya H, Noguchi R, Namisaki T, Moriya K, Uejima M, Kitade M, Mashitani T, Takeda K, Kawaratani H, Okura Y, Kaji K, Douhara A, Sawada Y, Nishimura N, Seki K, Mitoro A, Yamao J, Yoshiji H.
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Journal Title
World J Hepatol.
Volume: 8
Issue: 28
Pages: 1194-1194
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Ipragliflozin, a sodium-glucose cotransporter 2 inhibitor, ameliorates the development of liver fibrosis in diabetic Otsuka Long-Evans Tokushima fatty rats.2016
Author(s)
Nishimura N, Kitade M, Noguchi R, Namisaki T, Moriya K, Takeda K, Okura Y, Aihara Y, Douhara A, Kawaratani H, Asada K, Yoshiji H.
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Journal Title
J Gastroenterol.
Volume: 未定
Related Report
Peer Reviewed
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[Journal Article] Efficacy of alogliptin in preventing non-alcoholic fatty liver disease progression in patients with type 2 diabetes.2016
Author(s)
Mashitani T, Noguchi R, Okura Y, Namisaki T, Mitoro A, Ishii H, Nakatani T, Kikuchi E, Moriyasu H, Matsumoto M, Sato S, An T, Morita H, Aizawa S, Tokuoka Y, Ishikawa M, Matsumura Y, Ohira H, Kogure A, Noguchi K, Yoshiji H.
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Journal Title
Biomed Rep.
Volume: 4
Pages: 183-187
Related Report
Peer Reviewed / Open Access
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[Journal Article] Beneficial effects of combined ursodeoxycholic acid and angiotensin-II type 1 receptor blocker on hepatic fibrogenesis in a rat model of nonalcoholic steatohepatitis.2016
Author(s)
Namisaki T, Noguchi R, Moriya K, Kitade M, Aihara Y, Douhara A, Nishimura N, Takeda K, Okura Y, Kawaratani H, Takaya H, Seki K, Yoshiji H.
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Journal Title
J Gastroenterol.
Volume: 51
Pages: 162-172
Related Report
Peer Reviewed
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[Journal Article] Reduction of endotoxin attenuates liver fibrosis through suppression of hepatic stellate cell activation and remission of intestinal permeability in a rat non-alcoholic steatohepatitis model.2015
Author(s)
Douhara A, Moriya K, Yoshiji H, Noguchi R, Namisaki T, Kitade M, Kaji K, Aihara Y, Nishimura N, Takeda K, Okura Y, Kawaratani H, Fukui H.
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Journal Title
Mol Med Rep.
Volume: 11
Pages: 1693-1700
NAID
Related Report
Peer Reviewed
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