Role of the Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway in Regulating Alternative Splicing of Tissue Factor mRNA in Human Endothelial Cells
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- Eisenreich Andreas
- Charitè - Universitätsmedizin Berlin, Campus Benjamin Franklin, Centrum für Herz- und Kreislaufmedizin
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- Malz Ronny
- Charitè - Universitätsmedizin Berlin, Campus Benjamin Franklin, Centrum für Herz- und Kreislaufmedizin
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- Pepke Wojciech
- Charitè - Universitätsmedizin Berlin, Campus Benjamin Franklin, Centrum für Herz- und Kreislaufmedizin
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- Ayral Yunus
- Charitè - Universitätsmedizin Berlin, Campus Benjamin Franklin, Centrum für Herz- und Kreislaufmedizin
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- Poller Wolfgang
- Charitè - Universitätsmedizin Berlin, Campus Benjamin Franklin, Centrum für Herz- und Kreislaufmedizin
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- Schultheiss Heinz-Peter
- Charitè - Universitätsmedizin Berlin, Campus Benjamin Franklin, Centrum für Herz- und Kreislaufmedizin
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- Rauch Ursula
- Charitè - Universitätsmedizin Berlin, Campus Benjamin Franklin, Centrum für Herz- und Kreislaufmedizin
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Background: Tissue factor (TF) is the primary initiator of blood coagulation. In response to tumor necrosis factor (TNF)-α human umbilical vein endothelial cells (HUVECs) express 2 TF isoforms: a soluble alternatively spliced isoform (asHTF) and membrane-bound "full length" (fl)TF. How the differential TF isoform expression is regulated is still unknown. This study compared the impact of PI3K/Akt pathway inhibition on alternative splicing of TF in HUVECs, to the influence of transcriptional regulation by inhibiting nuclear factor κ B (NFκB). Methods and Results: The mRNA expression of TF isoforms was assessed by real-time PCR, the thrombogenic activity was measured by a chromogenic TF activity assay and the phosphorylation state of serine/arginine-rich (SR) proteins was analyzed by western blotting. Transfection of HUVECs was done 72 h before the inhibition experiments were performed. PI3K/Akt pathway inhibition reduced the mRNA expression of asHTF but not flTF. Inhibition of NFκB reduced the expression of both isoforms. Moreover, the PI3K/Akt pathway inhibition, but not that of NFκB, modified the phosphorylation of the SR proteins SRp75, SRp55 and SF2/ASF. Additionally, overexpression of SF2/ASF and SRp75 influenced the differential TF-isoform expression in HUVECs. Conclusions: The PI3K/Akt pathway modulates alternative splicing of TF in HUVECs, distinct from transcriptional regulation. (Circ J 2009; 73: 1746-1752)<br>
収録刊行物
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- Circulation Journal
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Circulation Journal 73 (9), 1746-1752, 2009
一般社団法人 日本循環器学会
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詳細情報 詳細情報について
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- CRID
- 1390282680079931648
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- NII論文ID
- 10025935355
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- NII書誌ID
- AA11591968
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- ISSN
- 13474820
- 13469843
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- Crossref
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可