Academic Journal
Jagged/Notch proteins promote endothelial‐mesenchymal transition‐mediated pulmonary arterial hypertension via upregulation of the expression of GATAs
| العنوان: | Jagged/Notch proteins promote endothelial‐mesenchymal transition‐mediated pulmonary arterial hypertension via upregulation of the expression of GATAs |
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| المؤلفون: | Lin, Kun‐Chen, Yeh, Jui‐Ning, Shao, Pei‐Lin, Chiang, John Y., Sung, Pei‐Hsun, Huang, Chi‐Ruei, Chen, Yi‐Ling, Yip, Hon‐Kan, Guo, Jun |
| المساهمون: | Chang Gung University |
| المصدر: | Journal of Cellular and Molecular Medicine ; volume 27, issue 8, page 1110-1130 ; ISSN 1582-1838 1582-4934 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2023 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | This study tested the hypothesis that Jagged2/Notches promoted the endothelial‐mesenchymal transition (endMT)‐mediated pulmonary arterial hypertension (PAH) (i.e. induction by monocrotaline [MCT]/63 mg/kg/subcutaneous injection) through increasing the expression of GATA‐binding factors which were inhibited by propylthiouracil (PTU) (i.e. 0.1% in water for daily drinking since Day 5 after PAH induction) in rodent. As compared with the control (i.e. HUVECs), the protein expressions of GATAs (3/4/6) and endMT markers (Snail/Zeb1/N‐cadherin/vimentin/fibronectin/α‐SMA/p‐Smad2) were significantly reduced, whereas the endothelial‐phenotype markers (CD31/E‐cadherin) were significantly increased in silenced JAG2 gene or in silenced GATA3 gene of HUVECs (all p < 0.001). As compared with the control, the protein expressions of intercellular signallings (GATAs [3/4/6], Jagged1/2, notch1/2 and Snail/Zeb1/N‐cadherin/vimentin/fibronectin/α‐SMA/p‐Smad2) were significantly upregulated in TGF‐ß/monocrotaline‐treated HUVECs that were significantly reversed by PTU treatment (all p < 0.001). By Day 42, the results of animal study demonstrated that the right‐ventricular systolic‐blood‐pressure (RVSBP), RV weight (RVW) and lung injury/fibrotic scores were significantly increased in MCT group than sham‐control (SC) that were reversed in MCT + PTU groups, whereas arterial oxygen saturation (%) and vasorelaxation/nitric oxide production of PA exhibited an opposite pattern of RVW among the groups (all p < 0.0001). The protein expressions of hypertrophic (ß‐MHC)/pressure‐overload (BNP)/oxidative‐stress (NOX‐1/NOX‐2) biomarkers in RV and the protein expressions of intercellular signalling (GATAs3/4/6, Jagged1/2, notch1/2) and endMT markers (Snail/Zeb1/N‐cadherin/vimentin/fibronectin/TGF‐ß/α‐SMA/p‐Smad2) in lung parenchyma displayed an identical pattern of RVW among the groups (all p < 0.0001). Jagged‐Notch‐GATAs signalling, endMT markers and RVSBP that were increased in PAH were suppressed by PTU. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1111/jcmm.17723 |
| الاتاحة: | http://dx.doi.org/10.1111/jcmm.17723 https://onlinelibrary.wiley.com/doi/pdf/10.1111/jcmm.17723 https://onlinelibrary.wiley.com/doi/full-xml/10.1111/jcmm.17723 |
| Rights: | http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.C58F7701 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1111/jcmm.17723 |
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