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Smoothened Regulates Migration of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via Activation of Rho GTPase Signaling
- Source :
- Frontiers in Immunology. 8
- Publication Year :
- 2017
- Publisher :
- Frontiers Media SA, 2017.
-
Abstract
- Fibroblast-like synoviocytes (FLSs) acquire aggressive phenotypes characterized with enhanced migration abilities and inherent invasive qualities in rheumatoid arthritis (RA). Smoothened (Smo) is a key component of sonic hedgehog (Shh) signaling and contributes to tumor cell invasion and metastasis. The objective of this study is to investigate the role of Smo in the modulation of cell migration and explore the underlying molecular mechanism(s). FLSs were isolated from RA synovium. Shh levels were regulated by a Smo agonist (purmorphamine), Smo antagonist (KAAD-cyclopamine), or small interfering RNA targeting the Smo gene (Smo-siRNA) in RA-FLSs. Expression of Smo was detected by real-time PCR and western blot analysis. Cell migration was examined by Transwell assay and activation of Rho GTPases was measured by pull-down assays. Incubation with purmorphamine resulted in a significant increase of cell migration and activation of Rho GTPase signaling compared to controls (P
- Subjects :
- rheumatoid arthritis
0301 basic medicine
Fibroblast-like synoviocyte
Purmorphamine
Immunology
Cell migration
GTPase
Biology
migration
Hedgehog signaling pathway
Cell biology
03 medical and health sciences
Smoothened Receptor
030104 developmental biology
sonic hedgehog signaling
biology.protein
Immunology and Allergy
fibroblast-like synoviocyte
Sonic hedgehog
Smoothened
smoothened protein
Subjects
Details
- ISSN :
- 16643224
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Frontiers in Immunology
- Accession number :
- edsair.doi.dedup.....fe7b677176b93c4b8962d03c87dda440