Expression and functional analysis of let-7 for the establishment of new diagnostic and therapeutic methods for liver fibrosis
Project/Area Number |
17K09435
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Gastroenterology
|
Research Institution | Nagoya City University |
Principal Investigator |
Matsuura Kentaro 名古屋市立大学, 医薬学総合研究院(医学), 講師 (30580576)
|
Project Period (FY) |
2017-04-01 – 2023-03-31
|
Project Status |
Completed (Fiscal Year 2022)
|
Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | 肝線維化 / microRNA / miRNA / let-7 |
Outline of Final Research Achievements |
Using stored samples from several chronic hepatitis C cohorts in Japan, we found that the expression level of let-7a in serum decreased with the progression of liver fibrosis and correlated well with other fibrosis markers. Cytokine and chemokine analysis was performed using stored sera from patients whose hepatitis C virus had been eliminated by treatment, and we found that serum Angiopoietin-2 and CXCL10 expression levels after completion of treatment were associated with subsequent improvement or deterioration of liver fibrosis. The expression level of let-7 in liver tissue was significantly decreased after activation of a human hepatic stellate cell line (LX-2) with several cytokines. When let-7 was transfected into LX-2, there was a trend toward suppression of gene expression related to inflammation and liver fibrosis.
|
Academic Significance and Societal Importance of the Research Achievements |
末梢血中のlet-7発現レベルが肝線維化診断マーカーとして応用できる可能性を見出した。血清サイトカイン・ケモカイン解析により、HCV排除後の肝線維化改善・非改善に関わる機構の解明につながることが期待される。細胞株を用いた検討から、let-7が肝線維化機構を抑制的に制御していること見出し、今後さらなる検討によりlet-7補充療法を肝線維化治療に応用できる可能性が考えられた。これらの期待される新規治療法は、HCV排除後や非アルコール性脂肪性肝疾患など極めて多くの患者が対象となり得、実現されればその社会的貢献は非常に大きい。
|
Report
(7 results)
Research Products
(29 results)
-
-
-
[Journal Article] Liver-related events after direct-acting antiviral therapy in patients with hepatitis C virus-associated cirrhosis2022
Author(s)
Tahata Y, Hikita H, Mochida S, Enomoto N, Kawada N, Kurosaki M, Ido A, Miki D, Yoshiji H, Takikawa Y, Sakamori R, Hiasa Y, Nakao K, Kato N, Ueno Y, Yatsuhashi H, Itoh Y, Tateishi R, Suda G, Takami T, Nakamoto Y, Asahina Y, et al.
-
Journal Title
Journal of Gastroenterology
Volume: 57
Issue: 2
Pages: 120-132
DOI
Related Report
Peer Reviewed
-
-
[Journal Article] A novel noninvasive formula for predicting cirrhosis in patients with chronic hepatitis C2021
Author(s)
Atsukawa M, Tsubota A, Kondo C, Uchida-Kobayashi S, Takaguchi K, Tsutsui A, Nozaki A, Chuma M, Hidaka I, Ishikawa T, Iwasa M, Tamai Y, Tobari M, Matsuura K, Nagura Y, Abe H, Kato K, Suzuki K, Okubo T, Arai T, Itokawa N, Toyoda H, Enomoto M, Tamori A, Tanaka Y, Kawada N, Takei Y, Iwakiri K.
-
Journal Title
PLOS ONE
Volume: 16
Issue: 9
Pages: e0257166-e0257166
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
[Journal Article] TLL1 variant associated with development of hepatocellular carcinoma after eradication of hepatitis C virus by interferon-free therapy.2019
Author(s)
Iio E, Matsuura K (co-first author), Shimada N, Atsukawa M, Itokawa N, Abe H, Kato K, Takaguchi K, Senoh T, Eguchi Y, Nomura H, Yoshizawa K, Kang JH, Matsui T, Hirashima N, Kusakabe A, Miyaki T, Fujiwara K, Matsunami K, Tsutsumi S, Iwakiri K, Tanaka Y.
-
Journal Title
J Gastroenterol.
Volume: 54
Issue: 4
Pages: 339-346
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
-
-
[Journal Article] Circulating let-7 levels in serum correlate with the severity of hepatic fibrosis in chronic hepatitis C.2018
Author(s)
Matsuura K, Aizawa N, Enomoto H, Nishiguchi S, Toyoda H, Kumada T, Iio E, Ito K, Ogawa S, Isogawa M, Alter HJ, Tanaka Y.
-
Journal Title
Open Forum Infct Dis.
Volume: 5
Issue: 11
Pages: 268-268
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] Circulating let-7 levels in serum and extracellular vesicles correlate with hepatic fibrosis progression in chronic hepatitis C2017
Author(s)
Kentaro Matsuura, Etsuko Iio, Nobuhiro Aizawa, Hirayuki Enomoto, Shuhei Nishiguchi, Hidenori Toyoda, Takashi Kumada, Kayoko Matsunami, Kei Fujiwara, Shunsuke Nojiri, Valeria De Giorgi, Richard Y. Wang, Kazi Salam, Aparna Vuppala, Robert D. Allison, Patrizia Farci, Harvey J. Alter, and Yasuhito Tanaka
Organizer
米国肝臓学会
Related Report
Int'l Joint Research