دورية أكاديمية
Syndecan-2 regulates PAD2 to exert antifibrotic effects on RA-ILD fibroblasts
| العنوان: | Syndecan-2 regulates PAD2 to exert antifibrotic effects on RA-ILD fibroblasts |
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| المؤلفون: | Konstantin Tsoyi, Anthony J. Esposito, Bo Sun, Ryan G. Bowen, Kevin Xiong, Fernando Poli, Rafael Cardenas, Sarah G. Chu, Xiaoliang Liang, Stefan W. Ryter, Christine Beeton, Tracy J. Doyle, Matthew J. Robertson, Lindsay J. Celada, Freddy Romero, Souheil Y. El-Chemaly, Mark A. Perrella, I.-Cheng Ho, Ivan O. Rosas |
| المصدر: | Scientific Reports, Vol 12, Iss 1, Pp 1-11 (2022) |
| بيانات النشر: | Nature Portfolio, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | Abstract Rheumatoid arthritis (RA)-associated interstitial lung disease (RA-ILD) is the most common pulmonary complication of RA, increasing morbidity and mortality. Anti-citrullinated protein antibodies have been associated with the development and progression of both RA and fibrotic lung disease; however, the role of protein citrullination in RA-ILD remains unclear. Here, we demonstrate that the expression of peptidylarginine deiminase 2 (PAD2), an enzyme that catalyzes protein citrullination, is increased in lung homogenates from subjects with RA-ILD and their lung fibroblasts. Chemical inhibition or genetic knockdown of PAD2 in RA-ILD fibroblasts attenuated their activation, marked by decreased myofibroblast differentiation, gel contraction, and extracellular matrix gene expression. Treatment of RA-ILD fibroblasts with the proteoglycan syndecan-2 (SDC2) yielded similar antifibrotic effects through regulation of PAD2 expression, phosphoinositide 3-kinase/Akt signaling, and Sp1 activation in a CD148-dependent manner. Furthermore, SDC2-transgenic mice exposed to bleomycin-induced lung injury in an inflammatory arthritis model expressed lower levels of PAD2 and were protected from the development of pulmonary fibrosis. Together, our results support a SDC2-sensitive profibrotic role for PAD2 in RA-ILD fibroblasts and identify PAD2 as a promising therapeutic target of RA-ILD. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-022-06678-7 |
| URL الوصول: | https://doaj.org/article/ec81a56a0af949f686db3bdeb3e61b1e |
| رقم الأكسشن: | edsdoj.81a56a0af949f686db3bdeb3e61b1e |
| 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/s41598-022-06678-7 |