| Project/Area Number |
24591108
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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 |
Circulatory organs internal medicine
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| Research Institution | Gunma University |
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Principal Investigator |
KOWASE Keiko 群馬大学, 医学(系)研究科(研究院), 講師 (50594264)
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| Co-Investigator(Kenkyū-buntansha) |
KURABAYASHI Masahiko 群馬大学, 大学院医学系研究科, 教授 (00215047)
NAKAHARA Takehiro 群馬大学, 大学院医学系研究科, 助教 (00599540)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 肺高血圧 / 肺高血圧症 |
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| Outline of Final Research Achievements |
We have previously shown that the protein inhibitor of activated STAT (PIAS)1 promotes TGFbeta-induced activation of SMC gene expression at least in part by promoting sumoylation. Here,we tested the hypothesis that Notch1-TGFbeta-PIAS1 axis promote pulmonary artery hypertension (PAH).An siRNA specific for PIAS1 and ubc9, an E2-ligase for sumoylation, inhibited TGFbeta- and Notch1-induced expression of SMC specific genes in cultured pulmonary artery smooth muscle cells (PASMC) as determined by real-time RT-PCR. Expression of osteoprotegerine（OPG）was also inhibited by siRNA specific for PIAS1 and ubc9. Moreover,overexpression of PIAS family increased OPG promoter activity. Immunohistochemistry of model mice for hypoxia-induced pulmonary hypertension revealed colocalized expression of TGFbetaRII、Notch1 and SMC marker in pulmonary artery, whereas SUMO1 and OPG were expressed in tracheal epithelial cell. These results could indicate that Notch1-TGFbeta-PIAS1 axis participate in PAH.
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