التفاصيل البيبلوغرافية
| العنوان: |
The BMP Receptor 2 in Pulmonary Arterial Hypertension: When and Where the Animal Model Matches the Patient |
| المؤلفون: |
Chris Happé, Kondababu Kurakula, Xiao-Qing Sun, Denielli da Silva Goncalves Bos, Nina Rol, Christophe Guignabert, Ly Tu, Ingrid Schalij, Karien C. Wiesmeijer, Olga Tura-Ceide, Anton Vonk Noordegraaf, Frances S. de Man, Harm Jan Bogaard, Marie-José Goumans |
| المصدر: |
Cells; Volume 9; Issue 6; Pages: 1422 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2020 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
pulmonary arterial hypertension, BMPR2, BMP and TGF-β signaling, animal models of pulmonary hypertension |
| الوصف: |
Background: Mutations in bone morphogenetic protein receptor type II (BMPR2) are leading to the development of hereditary pulmonary arterial hypertension (PAH). In non-hereditary forms of PAH, perturbations in the transforming growth factor-β (TGF-β)/BMP-axis are believed to cause deficient BMPR2 signaling by changes in receptor expression, the activity of the receptor and/or downstream signaling. To date, BMPR2 expression and its activity in the lungs of patients with non-hereditary PAH is poorly characterized. In recent decades, different animal models have been used to understand the role of BMPR2 signaling in PAH pathophysiology. Specifically, the monocrotaline (MCT) and Sugen–Hypoxia (SuHx) models are extensively used in interventional studies to examine if restoring BMPR2 signaling results in PAH disease reversal. While PAH is assumed to develop in patients over months or years, pulmonary hypertension in experimental animal models develops in days or weeks. It is therefore likely that modifications in BMP and TGF-β signaling in these models do not fully recapitulate those in patients. In order to determine the translational potential of the MCT and SuHx models, we analyzed the BMPR2 expression and activity in the lungs of rats with experimentally induced PAH and compared this to the BMPR2 expression and activity in the lungs of PAH patients. Methods: the BMPR2 expression was analyzed by Western blot analysis and immunofluorescence (IF) microscopy to determine the quantity and localization of the receptor in the lung tissue from normal control subjects and patients with hereditary or idiopathic PAH, as well as in the lungs of control rats and rats with MCT or SuHx-induced PAH. The activation of the BMP pathway was analyzed by determining the level and localization of phosphorylated Smad1/5/8 (pSmad 1/5/8), a downstream mediator of canonical BMPR2 signaling. Results: While BMPR2 and pSmad 1/5/8 expression levels were unaltered in whole lung lysates/homogenates from patients with hereditary and idiopathic ... |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| Relation: |
Cell Signaling; https://dx.doi.org/10.3390/cells9061422 |
| DOI: |
10.3390/cells9061422 |
| الاتاحة: |
https://doi.org/10.3390/cells9061422 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: |
edsbas.20A68D62 |
| قاعدة البيانات: |
BASE |