Intraarticular gene transfer of SPRY2 suppresses adjuvant-induced arthritis in rats

Verfasser / Beitragende:
[Wei Zhang, Jingying Zhu, Zhiyan Du, Jiyun Yu, Yuanji Xu, Fang Wang]
Ort, Verlag, Jahr:
2015
Enthalten in:
Applied Microbiology and Biotechnology, 99/16(2015-08-01), 6727-6735
Format:
Artikel (online)
ID: 605498199
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024 7 0 |a 10.1007/s00253-015-6618-x  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s00253-015-6618-x 
245 0 0 |a Intraarticular gene transfer of SPRY2 suppresses adjuvant-induced arthritis in rats  |h [Elektronische Daten]  |c [Wei Zhang, Jingying Zhu, Zhiyan Du, Jiyun Yu, Yuanji Xu, Fang Wang] 
520 3 |a AKT and ERK pathways have been implicated as therapeutic targets for human rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) inhibition, and thus RA treatment. Sprouty2 (SPRY2) has been known as a tumor suppressor by blocking both ERK and AKT signaling cascades. Whether SPRY2 can function as a suppressor of tumor-like inflammatory FLS and RA through negatively regulating AKT and ERK activation has not been reported. The purpose of this study was to determine whether SPRY2 might have antiarthritic effects in experimental animal model of RA. We first determined that expression of SPRY2 mRNA was decreased in FLS from patients with RA compared with patients with osteoarthritis (OA). Further studies demonstrated that intraarticular gene transfer with AdSPRY2, the recombinant adenovirus containing SPRY2 complementary DNA, resulted in a significant suppression of rat adjuvant-induced arthritis (AIA) compared with the control AdGFP, the adenoviral vector encoding green fluorescent protein, as reflected in both clinical and histological observations. AdSPRY2 suppressed the production of proinflammatory cytokines and matrix metalloproteinases (MMPs), and the activation of ERK and AKT signals in AIA ankle joints. These results suggest that using SPRY2 to block the AKT and ERK pathways effectively reduces the inflammatory responses and arthritic progression in AIA. Thus, the development of an immunoregulatory strategy based on SPRY2 may therefore have therapeutic potential in the treatment of RA. 
540 |a Springer-Verlag Berlin Heidelberg, 2015 
690 7 |a SPRY2  |2 nationallicence 
690 7 |a Rheumatoid arthritis  |2 nationallicence 
690 7 |a Gene therapy  |2 nationallicence 
690 7 |a Inflammatory signals  |2 nationallicence 
690 7 |a Inflammatory mediators  |2 nationallicence 
700 1 |a Zhang  |D Wei  |u Department of Translational Medicine, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, 100850, Beijing, China  |4 aut 
700 1 |a Zhu  |D Jingying  |u Department of Translational Medicine, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, 100850, Beijing, China  |4 aut 
700 1 |a Du  |D Zhiyan  |u Department of Translational Medicine, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, 100850, Beijing, China  |4 aut 
700 1 |a Yu  |D Jiyun  |u Department of Translational Medicine, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, 100850, Beijing, China  |4 aut 
700 1 |a Xu  |D Yuanji  |u Department of Translational Medicine, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, 100850, Beijing, China  |4 aut 
700 1 |a Wang  |D Fang  |u Department of Translational Medicine, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, 100850, Beijing, China  |4 aut 
773 0 |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/16(2015-08-01), 6727-6735  |x 0175-7598  |q 99:16<6727  |1 2015  |2 99  |o 253 
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900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00253-015-6618-x  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Zhang  |D Wei  |u Department of Translational Medicine, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, 100850, Beijing, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Zhu  |D Jingying  |u Department of Translational Medicine, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, 100850, Beijing, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Du  |D Zhiyan  |u Department of Translational Medicine, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, 100850, Beijing, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Yu  |D Jiyun  |u Department of Translational Medicine, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, 100850, Beijing, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Xu  |D Yuanji  |u Department of Translational Medicine, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, 100850, Beijing, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Wang  |D Fang  |u Department of Translational Medicine, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, 100850, Beijing, China  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/16(2015-08-01), 6727-6735  |x 0175-7598  |q 99:16<6727  |1 2015  |2 99  |o 253