دورية أكاديمية
Chronic activation of human cardiac fibroblasts in vitro attenuates the reversibility of the myofibroblast phenotype
| العنوان: | Chronic activation of human cardiac fibroblasts in vitro attenuates the reversibility of the myofibroblast phenotype |
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| المؤلفون: | Caitlin Hall, Jonathan P. Law, Jasmeet S. Reyat, Max J. Cumberland, Shaun Hang, Nguyen T. N. Vo, Kavita Raniga, Chris J. Weston, Christopher O’Shea, Jonathan N. Townend, Katja Gehmlich, Charles J. Ferro, Chris Denning, Davor Pavlovic |
| المصدر: | Scientific Reports, Vol 13, Iss 1, Pp 1-14 (2023) |
| بيانات النشر: | Nature Portfolio, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | Abstract Activation of cardiac fibroblasts and differentiation to myofibroblasts underlies development of pathological cardiac fibrosis, leading to arrhythmias and heart failure. Myofibroblasts are characterised by increased α-smooth muscle actin (α-SMA) fibre expression, secretion of collagens and changes in proliferation. Transforming growth factor-beta (TGF-β) and increased mechanical stress can initiate myofibroblast activation. Reversibility of the myofibroblast phenotype has been observed in murine cells but has not been explored in human cardiac fibroblasts. In this study, chronically activated adult primary human ventricular cardiac fibroblasts and human induced pluripotent stem cell derived cFbs (hiPSC-cFbs) were used to investigate the potential for reversal of the myofibroblast phenotype using either subculture on soft substrates or TGF-β receptor inhibition. Culture on softer plates (25 or 2 kPa Young’s modulus) did not alter proliferation or reduce expression of α-SMA and collagen 1. Similarly, culture of myofibroblasts in the presence of TGF-β inhibitor did not reverse myofibroblasts back to a quiescent phenotype. Chronically activated hiPSC-cFbs also showed attenuated response to TGF-β receptor inhibition and inability to reverse to quiescent fibroblast phenotype. Our data demonstrate substantial loss of TGF-β signalling plasticity as well as a loss of feedback from the surrounding mechanical environment in chronically activated human myofibroblasts. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-023-39369-y |
| URL الوصول: | https://doaj.org/article/0120de0a24174c8798d8cc3427fd584c |
| رقم الأكسشن: | edsdoj.0120de0a24174c8798d8cc3427fd584c |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-023-39369-y |