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KAKEN_17K10153seika.pdf
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Title |
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肺血管発生と肺高血圧症におけるTbx4の役割
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Kana |
ハイ ケッカン ハッセイ ト ハイ コウケツアツショウ ニ オケル Tbx4 ノ ヤクワリ
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Hai kekkan hassei to hai kōketsuatsushō ni okeru Tbx4 no yakuwari
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Roles of Tbx4 for pulmonary vascular development and pulmonary hypertension
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内田, 敬子
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ウチダ, ケイコ
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Uchida, Keiko
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慶應義塾大学・保健管理センター (日吉) ・准教授
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Research team head
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科研費研究者番号 : 50286522
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山岸, 敬幸
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ヤマギシ, ヒロユキ
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Yamagishi, Hiroyuki
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Collaborator
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2021
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科学研究費補助金研究成果報告書
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2020
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肺血管発生の詳細は不明な点が多い。肺血管を構成する内皮細胞や平滑筋細胞の起源の候補と考えられている肺間葉系細胞には転写因子Tbx4が比較的高く発現しているが、肺血管発生におけるTbx4の役割は不明である。また、近年小児期発症の肺動脈性肺高血圧症でTBX4遺伝子変異が検出されたが、その発症機序は不明である。
本研究ではTbx4に着目し、胎生期の肺間葉系細胞でTbx4の発現を低下させたところ内皮様の管腔形成能が促進され、肺器官培養でTbx4の発現を低下させたところ肺発生が抑制された。肺間葉系細胞のTbx4は肺の発生や肺動脈性肺高血圧症の病態に関与する可能性が示唆された。
One of the transcription factors which are crucial for organogenesis, Tbx4, is highly expressed in the lung mesenchyme. Lung mesenchyme consists of undifferentiated progenitor cells, which give rise to various cell types, possibly including pulmonary vascular cells. Recently TBX4 mutations have reported in patients with PAH. However, the mechanisms of pulmonary vascular development and pathogenesis of pulmonary arterial hypertension (PAH) remain unclear.
We found that Tbx4 knockdown in lung mesenchymal cells facilitated tube formation activity, which is characteristic of endothelial cells, and that Tbx4 knockdown in lung organ culture inhibited lung development. Our results suggest that Tbx4 in undifferentiated mesenchymal progenitor cells may be involved in the formation of both airways and vessels in the lungs. The roles of Tbx4 in the lung mesenchyme may pave the way for novel mechanisms underlying pulmonary vascular development and pathogenesis of PAH.
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研究種目 : 基盤研究 (C) (一般)
研究期間 : 2017~2020
課題番号 : 17K10153
研究分野 : 心血管発生
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