Proteasome activator PA200 regulates myofibroblast differentiation
| العنوان: | Proteasome activator PA200 regulates myofibroblast differentiation |
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| المؤلفون: | Thomas Meul, Shrikant R. Mulay, Martina Korfei, Isis E. Fernandez, Andrea C. Schamberger, Oliver Eickelberg, Andreas Günther, Christina Lukas, Hans-Joachim Anders, Jürgen Behr, Nora Semren, Vanessa Welk, Ilona Kammerl, Silke Meiners |
| المصدر: | Scientific Reports, Vol 9, Iss 1, Pp 1-11 (2019) Scientific Reports Sci. Rep. 9:15224 (2019) |
| بيانات النشر: | Nature Publishing Group, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Adult, Male, Proteasome Endopeptidase Complex, lcsh:Medicine, Kidney, Article, Mice, Idiopathic pulmonary fibrosis, Downregulation and upregulation, Transforming Growth Factor beta, Fibrosis, medicine, Animals, Humans, Gene silencing, Myofibroblasts, lcsh:Science, Lung, Cells, Cultured, Respiratory tract diseases, Multidisciplinary, Molecular medicine, Chemistry, Activator (genetics), lcsh:R, Protein turnover, Nuclear Proteins, Cell Differentiation, Middle Aged, medicine.disease, Idiopathic Pulmonary Fibrosis, Cell biology, Mice, Inbred C57BL, Proteasome, Female, lcsh:Q, Myofibroblast, Signal Transduction |
| الوصف: | The proteasome is essential for the selective degradation of most cellular proteins and is fine-tuned according to cellular needs. Proteasome activators serve as building blocks to adjust protein turnover in cell growth and differentiation. Understanding the cellular function of proteasome activation in more detail offers a new strategy for therapeutic targeting of proteasomal protein breakdown in disease. The role of the proteasome activator PA200 in cell function and its regulation in disease is unknown. In this study, we investigated the function of PA200 in myofibroblast differentiation and fibrotic tissue remodeling. PA200 was upregulated in hyperplastic basal cells and myofibroblasts of fibrotic lungs from patients with idiopathic pulmonary fibrosis. Increased expression of PA200 and enhanced formation of PA200-proteasome complexes was also evident in experimental fibrosis of the lung and kidney in vivo and in activated primary human myofibroblasts of the lung in vitro. Transient silencing and overexpression revealed that PA200 functions as a negative regulator of myofibroblast differentiation of human but not mouse cells. Our data thus suggest an unexpected and important role for PA200 in adjusting myofibroblast activation in response to pro-fibrotic stimuli, which fails in idiopathic pulmonary fibrosis. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2045-2322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b2a9caaad77f1669d579727f0e12caa1 http://link.springer.com/article/10.1038/s41598-019-51665-0 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....b2a9caaad77f1669d579727f0e12caa1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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