Functional expression of TMEM16 channels in portal hypertension
| Project/Area Number |
16K08278
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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 |
Pharmacology in pharmacy
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| Research Institution | Nagoya City University |
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Principal Investigator |
YAMAMURA Hisao 名古屋市立大学, 大学院薬学研究科, 教授 (80398362)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | TMEM16A / 門脈圧亢進症 / クロライドチャネル / カルシウム / 門脈 / 平滑筋 / 肝硬変 / 線維化 / アンジオテンシンⅡ / ビリルビン / カルシウム活性化クロライドチャネル |
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| Outline of Final Research Achievements |
Portal hypertension is a major complication in patients with chronic liver diseases and cirrhosis, but its pathogenic mechanism remains unclear. Here, we demonstrate that, in portal hypertensive mice, 1) expression of calcium-activated chloride channel TMEM16A is downregulated, 2) calcium-activated chloride currents are reduced, and 3) component of TMEM16A-mediated contraction is attenuated. These results suggest that TMEM16A is involved in the molecular mechanism of the development of portal hypertension.
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| Academic Significance and Societal Importance of the Research Achievements |
門脈圧亢進症とは門脈圧が亢進する疾患群の総称であり、その約80%は肝硬変に伴って発症する。しかし、その病態形成メカニズムには未解明な部分が多いため、門脈圧亢進症に対する根本的な治療法は確立していない。そのため、本研究課題で明らかになった、門脈圧亢進症でのカルシウム活性化クロライドチャネルTMEM16Aの発現低下は、門脈圧亢進症の病態形成機構の解明および新規治療薬の標的創薬につながることが期待される。
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Report
(4 results)
Research Products
(121 results)
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[Journal Article] Capsaicin-induced Ca2+ signaling is enhanced via upregulated TRPV1 channels in pulmonary artery smooth muscle cells from patients with idiopathic PAH.2017
Author(s)
Song S, Ayon RJ, Yamamura A, Yamamura H, Dash S, Babicheva A, Tang H, Sun X, Cordery AG, Khalpey Z, Black SM, Desai AA, Rischard F, McDermott KM, Garcia JG, Makino A, Yuan JX.
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Journal Title
Am J Physiol Lung Cell Mol Physiol.
Volume: 312(3)
Issue: 3
Pages: L309-L325
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Pathogenic role of calcium-sensing receptors in the development and progression of pulmonary hypertension.2016
Author(s)
Tang H, Yamamura A, Yamamura H, Song S, Fraidenburg DR, Chen J, Gu Y, Pohl NM, Zhou T, Jiménez-Pérez L, Ayon RJ, Desai AA, Goltzman D, Rischard F, Khalpey ZI, Black SM, Garcia JG, Makino A, Yuan JX.
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Journal Title
Am J Physiol Lung Cell Mol Physiol.
Volume: in press
Issue: 9
Pages: L846-L859
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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