| Project/Area Number |
15K09152
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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 |
Cardiovascular medicine
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| Research Institution | Gunma University |
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Principal Investigator |
Kowase Keiko 群馬大学, 大学院医学系研究科, 講師 (50594264)
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| Co-Investigator(Kenkyū-buntansha) |
倉林 正彦 群馬大学, 大学院医学系研究科, 教授 (00215047)
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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 |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 肺高血圧症 / 肺高血圧 / 血管平滑筋 / 分子血管学 |
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| Outline of Final Research Achievements |
We have previously shown that the protein inhibitor of activated STAT (PIAS)1 promotes TGFb-induced activation of SMC gene expression at least in part by promoting sumoylaton. Here, we tested the hypothesis that PIAS1 and sumoylation promote pulmonary artery hypertension (PAH). An siRNA specific for PIAS1 and ubc9, an E2-ligase for sumoylation, inhibited TGFb- 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 and SRF increased OPG promoter activity. Immunohistochemistry of model mice for pulmonary hypertension revealed colocalized expression of TGFbRII, Notch1 and SMC markers in pulmonary artery, whereas SUMO1, OPG and ubc9 were expressed in tracheal epithelial cells. These results could indicate that sumoylation participated in PAH through OPG gene expression.
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