論文 - 詳細
| RRC ID | 66027 |
|---|---|
| 著者 | Boezio GL, Bensimon-Brito A, Piesker J, Guenther S, Helker CS, Stainier DY. |
| タイトル | Endothelial TGF-β signaling instructs smooth muscle cell development in the cardiac outflow tract. |
| ジャーナル | Elife |
| Abstract |
The development of the cardiac outflow tract (OFT), which connects the heart to the great arteries, relies on a complex crosstalk between endothelial (ECs) and smooth muscle (SMCs) cells. Defects in OFT development can lead to severe malformations, including aortic aneurysms, which are frequently associated with impaired TGF-β signaling. To better understand the role of TGF-β signaling in OFT formation, we generated zebrafish lacking the TGF-β receptor Alk5 and found a strikingly specific dilation of the OFT: alk5-/- OFTs exhibit increased EC numbers as well as extracellular matrix (ECM) and SMC disorganization. Surprisingly, endothelial-specific alk5 overexpression in alk5-/- rescues the EC, ECM, and SMC defects. Transcriptomic analyses reveal downregulation of the ECM gene fibulin-5, which when overexpressed in ECs ameliorates OFT morphology and function. These findings reveal a new requirement for endothelial TGF-β signaling in OFT morphogenesis and suggest an important role for the endothelium in the etiology of aortic malformations. |
| 巻・号 | 9 |
| 公開日 | 2020-9-29 |
| DOI | 10.7554/eLife.57603 |
| PII | 57603 |
| PMID | 32990594 |
| PMC | PMC7524555 |
| MeSH | Animals Aorta / cytology Aorta / metabolism Endothelium, Vascular / cytology Endothelium, Vascular / metabolism* Heart Ventricles / cytology Heart Ventricles / metabolism Myocytes, Smooth Muscle / metabolism* Receptor, Transforming Growth Factor-beta Type I / metabolism Smad3 Protein / metabolism Transforming Growth Factor beta / metabolism* Zebrafish Zebrafish Proteins / metabolism |
| IF | 7.08 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 44 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ゼブラフィッシュ | TgBAC(pdgfrb:EGFP)ncv22Tg |