2022 Fiscal Year Final Research Report
Exploring novel proangiogenic factors of pulmonary artery using a LacZ reporter mouse for pulmonary artery smooth muscle
Project/Area Number |
20K08267
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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 |
Review Section |
Basic Section 52050:Embryonic medicine and pediatrics-related
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Research Institution | Keio University |
Principal Investigator |
UCHIDA Keiko 慶應義塾大学, 保健管理センター(日吉), 准教授 (50286522)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | 肺動脈発生 / 先天性心疾患 / 平滑筋 / 遺伝子改変マウス |
Outline of Final Research Achievements |
Hypoplasia of pulmonary arteries, a frequent complication of cyanotic congenital heart disease, is a poor prognostic factor with no effective treatment. The aim of this study was to elucidate the mechanism of pulmonary artery development in order to develop any targets of the treatment for their hypoplasia. We found that the expression of Tbx4, one of the disease-causing genes for pulmonary arterial hypertension, was suppressed by antisense oligonucleotides (AS) in a lung organ culture system, resulting in suppression of airway branching and maturation of vascular endothelium in the lungs. In addition, a genetic analysis applied to the family members including patients with congenital complex heart disease found the compound variations of the two genes as a candidate cause of the disease caused not only was cardiac development impairment, but the pulmonary arteriogram of fetal lungs was also characterized, suggesting an effect on pulmonary vascular development.
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Free Research Field |
小児循環器
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Academic Significance and Societal Importance of the Research Achievements |
小児循環器の医療現場で遭遇するチアノーゼ性心疾患にはしばしば肺動脈低形成が合併する。肺動脈低形成には有効な治療法がないために手術適応をも左右する予後不良因子である。心臓発生においては分子レベルでの基礎研究が比較的進んでいる一方で、肺血管発生の発生は肺血管細胞の系譜を含めて不明な点が多い。本研究は、小児循環器の臨床で遭遇する二つの疾患、肺高血圧症と単心室を含む先天性複雑性心疾患の疾患原因遺伝子の発現を抑制した肺やマウス個体を、私たちが独自に開発した肺動脈標識技術を用いて観察し、肺動脈発生に関与する知見を得たこと学術的意義がある。
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