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J Immunol Res. 2014;2014:401903. doi: 10.1155/2014/401903. Epub 2014 Mar 6.

Sonic hedgehog signaling drives proliferation of synoviocytes in rheumatoid arthritis: a possible novel therapeutic target.

Author information

1
School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China ; Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China ; Department of Rheumatology of Zhongshan Affiliated Hospital, Sun Yat-Sen University, Zhongshan, Guangdong 528400, China.
2
Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China.
3
School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.

Abstract

Sonic hedgehog (Shh) signaling controls many aspects of human development, regulates cell growth and differentiation in adult tissues, and is activated in a number of malignancies. Rheumatoid arthritis (RA) is characterized by chronic synovitis and pannus formation associated with activation of fibroblast-like synoviocytes (FLS). We investigated whether Shh signaling plays a role in the proliferation of FLS in RA. Expression of Shh signaling related components (Shh, Ptch1, Smo, and Gli1) in RA synovial tissues was examined by immunohistochemistry (IHC) and in FLS by IHC, immunofluorescence (IF), quantitative RT-PCR, and western blotting. Expression of Shh, Smo, and Gli1 in RA synovial tissue was higher than that in control tissue (P < 0.05). Cyclopamine (a specific inhibitor of Shh signaling) decreased mRNA expression of Shh, Ptch1, Smo, and Gli1 in cultured RA FLS, Shh, and Smo protein expression, and significantly decreased FLS proliferation. Flow cytometry analysis suggested that cyclopamine treatment resulted in cell cycle arrest of FLS in G1 phase. Our data show that Shh signaling is activated in synovium of RA patients in vivo and in cultured FLS form RA patients in vitro, suggesting a role in the proliferation of FLS in RA. It may therefore be a novel therapeutic target in RA.

PMID:
24741597
PMCID:
PMC3987882
DOI:
10.1155/2014/401903
[Indexed for MEDLINE]
Free PMC Article

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