Sonic Hedgehog Signaling Drives Proliferation of Synoviocytes in Rheumatoid Arthritis: A Possible Novel Therapeutic Target
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 fibr...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2014/401903 |
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| author | Mingxia Wang Shangling Zhu Weixiang Peng Qiuxia Li Zhaoxia Li Minqi Luo Xiaoxue Feng Zhuofeng Lin Jianlin Huang |
| author_facet | Mingxia Wang Shangling Zhu Weixiang Peng Qiuxia Li Zhaoxia Li Minqi Luo Xiaoxue Feng Zhuofeng Lin Jianlin Huang |
| author_sort | Mingxia Wang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1778f482480541a69f8d3b7a2653ca61 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-1778f482480541a69f8d3b7a2653ca612025-02-03T01:32:47ZengWileyJournal of Immunology Research2314-88612314-71562014-01-01201410.1155/2014/401903401903Sonic Hedgehog Signaling Drives Proliferation of Synoviocytes in Rheumatoid Arthritis: A Possible Novel Therapeutic TargetMingxia Wang0Shangling Zhu1Weixiang Peng2Qiuxia Li3Zhaoxia Li4Minqi Luo5Xiaoxue Feng6Zhuofeng Lin7Jianlin Huang8School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, ChinaDepartment of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, ChinaDepartment of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, ChinaDepartment of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, ChinaDepartment of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, ChinaDepartment of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, ChinaDepartment of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, ChinaDepartment of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, ChinaSonic 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.http://dx.doi.org/10.1155/2014/401903 |
| spellingShingle | Mingxia Wang Shangling Zhu Weixiang Peng Qiuxia Li Zhaoxia Li Minqi Luo Xiaoxue Feng Zhuofeng Lin Jianlin Huang Sonic Hedgehog Signaling Drives Proliferation of Synoviocytes in Rheumatoid Arthritis: A Possible Novel Therapeutic Target Journal of Immunology Research |
| title | Sonic Hedgehog Signaling Drives Proliferation of Synoviocytes in Rheumatoid Arthritis: A Possible Novel Therapeutic Target |
| title_full | Sonic Hedgehog Signaling Drives Proliferation of Synoviocytes in Rheumatoid Arthritis: A Possible Novel Therapeutic Target |
| title_fullStr | Sonic Hedgehog Signaling Drives Proliferation of Synoviocytes in Rheumatoid Arthritis: A Possible Novel Therapeutic Target |
| title_full_unstemmed | Sonic Hedgehog Signaling Drives Proliferation of Synoviocytes in Rheumatoid Arthritis: A Possible Novel Therapeutic Target |
| title_short | Sonic Hedgehog Signaling Drives Proliferation of Synoviocytes in Rheumatoid Arthritis: A Possible Novel Therapeutic Target |
| title_sort | sonic hedgehog signaling drives proliferation of synoviocytes in rheumatoid arthritis a possible novel therapeutic target |
| url | http://dx.doi.org/10.1155/2014/401903 |
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