Cyclic GMP-AMP Synthase Is Required for Cell Proliferation and Inflammatory Responses in Rheumatoid Arthritis Synoviocytes
Rheumatoid arthritis (RA) is characterized by inflammatory cell infiltration, fibroblast-like synoviocytes (FLS) invasive proliferation, and joint destruction. Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that induces immune activation. In this study, we examined whether cGAS plays a rol...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2015/192329 |
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| author | Yan Wang Guo-Hua Su Fang Zhang Jing-Xue Chu Yun-Shan Wang |
| author_facet | Yan Wang Guo-Hua Su Fang Zhang Jing-Xue Chu Yun-Shan Wang |
| author_sort | Yan Wang |
| collection | DOAJ |
| description | Rheumatoid arthritis (RA) is characterized by inflammatory cell infiltration, fibroblast-like synoviocytes (FLS) invasive proliferation, and joint destruction. Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that induces immune activation. In this study, we examined whether cGAS plays a role in RA FLS. In this study, cGAS was overexpressed in RA-FLS compared with OA FLS. TNFα stimulation induced cGAS expression in RA FLS. Overexpression of cGAS promoted the proliferation and knockdown of cGAS inhibited the proliferation of RA FLS. cGAS overexpression enhanced the production of proinflammatory cytokines and matrix metalloproteinases (MMPs) as well as AKT and ERK phosphorylation in TNFα-stimulated FLS. In contrast, cGAS silencing inhibited production of proinflammatory cytokines and matrix metalloproteinases (MMPs) as well as AKT and ERK phosphorylation in TNFα-stimulated FLS. These results suggest that cGAS activates the AKT and ERK pathways to promote the inflammatory response of RA FLS, and the development of strategies targeting cGAS may have therapeutic potential for human RA. |
| format | Article |
| id | doaj-art-65277f93b04a46179fdb1f4e7b0cba9f |
| institution | OA Journals |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-65277f93b04a46179fdb1f4e7b0cba9f2025-08-20T02:06:36ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/192329192329Cyclic GMP-AMP Synthase Is Required for Cell Proliferation and Inflammatory Responses in Rheumatoid Arthritis SynoviocytesYan Wang0Guo-Hua Su1Fang Zhang2Jing-Xue Chu3Yun-Shan Wang4The Medical Laboratory Diagnostics Center, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, ChinaDepartment of Bone and Joint Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, ChinaThe Medical Laboratory Diagnostics Center, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, ChinaThe Medical Laboratory Diagnostics Center, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, ChinaThe Medical Laboratory Diagnostics Center, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, ChinaRheumatoid arthritis (RA) is characterized by inflammatory cell infiltration, fibroblast-like synoviocytes (FLS) invasive proliferation, and joint destruction. Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that induces immune activation. In this study, we examined whether cGAS plays a role in RA FLS. In this study, cGAS was overexpressed in RA-FLS compared with OA FLS. TNFα stimulation induced cGAS expression in RA FLS. Overexpression of cGAS promoted the proliferation and knockdown of cGAS inhibited the proliferation of RA FLS. cGAS overexpression enhanced the production of proinflammatory cytokines and matrix metalloproteinases (MMPs) as well as AKT and ERK phosphorylation in TNFα-stimulated FLS. In contrast, cGAS silencing inhibited production of proinflammatory cytokines and matrix metalloproteinases (MMPs) as well as AKT and ERK phosphorylation in TNFα-stimulated FLS. These results suggest that cGAS activates the AKT and ERK pathways to promote the inflammatory response of RA FLS, and the development of strategies targeting cGAS may have therapeutic potential for human RA.http://dx.doi.org/10.1155/2015/192329 |
| spellingShingle | Yan Wang Guo-Hua Su Fang Zhang Jing-Xue Chu Yun-Shan Wang Cyclic GMP-AMP Synthase Is Required for Cell Proliferation and Inflammatory Responses in Rheumatoid Arthritis Synoviocytes Mediators of Inflammation |
| title | Cyclic GMP-AMP Synthase Is Required for Cell Proliferation and Inflammatory Responses in Rheumatoid Arthritis Synoviocytes |
| title_full | Cyclic GMP-AMP Synthase Is Required for Cell Proliferation and Inflammatory Responses in Rheumatoid Arthritis Synoviocytes |
| title_fullStr | Cyclic GMP-AMP Synthase Is Required for Cell Proliferation and Inflammatory Responses in Rheumatoid Arthritis Synoviocytes |
| title_full_unstemmed | Cyclic GMP-AMP Synthase Is Required for Cell Proliferation and Inflammatory Responses in Rheumatoid Arthritis Synoviocytes |
| title_short | Cyclic GMP-AMP Synthase Is Required for Cell Proliferation and Inflammatory Responses in Rheumatoid Arthritis Synoviocytes |
| title_sort | cyclic gmp amp synthase is required for cell proliferation and inflammatory responses in rheumatoid arthritis synoviocytes |
| url | http://dx.doi.org/10.1155/2015/192329 |
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