Academic Journal
PPARγ agonist rosiglitazone inhibits migration and invasion by downregulating Cyr61 in rheumatoid arthritis fibroblast‐like synoviocytes
| العنوان: | PPARγ agonist rosiglitazone inhibits migration and invasion by downregulating Cyr61 in rheumatoid arthritis fibroblast‐like synoviocytes |
|---|---|
| المؤلفون: | Kwon, Eun‐Jeong, Park, Eun‐Jung, Choi, Sungwook, Kim, Sang‐Rim, Cho, Moonjae, Kim, Jinseok |
| المساهمون: | Jeju National University Hospital |
| المصدر: | International Journal of Rheumatic Diseases ; volume 20, issue 10, page 1499-1509 ; ISSN 1756-1841 1756-185X |
| بيانات النشر: | Wiley |
| سنة النشر: | 2016 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | Aim Peroxisome proliferator‐activated receptor gamma ( PPAR γ) agonists have anti‐inflammatory properties that reduce inflammatory cytokine production in rheumatoid arthritis ( RA ). Cysteine‐rich angiogenic inducer 61 (Cyr61) is associated with diseases related to chronic inflammation. The aim of this study was to investigate the mechanisms underlying the effects of PPAR γ agonists on tumor necrosis factor ( TNF )‐α‐induced fibroblast‐like synoviocyte ( FLS ) invasion and migration, as well as Cyr61 production, in RA ‐ FLS . Methods FLS were cultured with TNF ‐α and Cyr61 in the presence or absence of PPAR γ agonists. Matrix metalloproteinase and Cyr61 expression levels in RA ‐ FLS and culture supernatants were measured by reverse transcriptase–polymerase chain reaction ( RT ‐ PCR ) and Western blotting. The migration and invasion phenotypes of RA ‐ FLS were determined by wound healing and Boyden chamber assays. Results Cyr61 protein was expressed in RA ‐ FLS , and its intracellular expression and secretion levels were increased by TNF ‐α. Moreover, Cyr61 directly promoted RA ‐ FLS migration and invasion. Rosiglitazone ( RSG ) significantly decreased TNF ‐α‐induced Cyr61 expression. RSG decreased TNF ‐α‐induced nuclear factor ( NF )‐κB activation and inhibitor of κBα degradation. Furthermore, RSG inhibited TNF ‐α‐induced RA ‐ FLS migration and invasion and decreased Cyr61 treatment‐induced RA ‐ FLS invasion. Finally, blocking Cyr61 significantly attenuated TNF ‐α‐induced migration. Conclusions Our results demonstrate for the first time that PPAR γ agonists may have beneficial effects on the migration and invasion of RA ‐ FLS via the downregulation of Cyr61. Therefore, PPAR γ agonists could be potential treatment targets for RA . |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1111/1756-185x.12913 |
| DOI: | 10.1111/1756-185X.12913 |
| الاتاحة: | http://dx.doi.org/10.1111/1756-185x.12913 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2F1756-185X.12913 https://onlinelibrary.wiley.com/doi/pdf/10.1111/1756-185X.12913 |
| Rights: | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| رقم الانضمام: | edsbas.EEFDA912 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1111/1756-185x.12913 |
|---|