caa a22 4500 605498199 CHVBK 20210128100545.0 cr unu---uuuuu 210128e20150801xx s 000 0 eng 10.1007/s00253-015-6618-x doi (NATIONALLICENCE)springer-10.1007/s00253-015-6618-x Intraarticular gene transfer of SPRY2 suppresses adjuvant-induced arthritis in rats [Elektronische Daten] [Wei Zhang, Jingying Zhu, Zhiyan Du, Jiyun Yu, Yuanji Xu, Fang Wang] 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. Springer-Verlag Berlin Heidelberg, 2015 SPRY2 nationallicence Rheumatoid arthritis nationallicence Gene therapy nationallicence Inflammatory signals nationallicence Inflammatory mediators nationallicence Zhang Wei Department of Translational Medicine, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, 100850, Beijing, China aut Zhu Jingying Department of Translational Medicine, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, 100850, Beijing, China aut Du Zhiyan Department of Translational Medicine, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, 100850, Beijing, China aut Yu Jiyun Department of Translational Medicine, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, 100850, Beijing, China aut Xu Yuanji Department of Translational Medicine, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, 100850, Beijing, China aut Wang Fang Department of Translational Medicine, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, 100850, Beijing, China aut Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/16(2015-08-01), 6727-6735 0175-7598 99:16<6727 2015 99 253 https://doi.org/10.1007/s00253-015-6618-x text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00253-015-6618-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhang Wei Department of Translational Medicine, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, 100850, Beijing, China aut NATIONALLICENCE 700 1- Zhu Jingying Department of Translational Medicine, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, 100850, Beijing, China aut NATIONALLICENCE 700 1- Du Zhiyan Department of Translational Medicine, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, 100850, Beijing, China aut NATIONALLICENCE 700 1- Yu Jiyun Department of Translational Medicine, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, 100850, Beijing, China aut NATIONALLICENCE 700 1- Xu Yuanji Department of Translational Medicine, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, 100850, Beijing, China aut NATIONALLICENCE 700 1- Wang Fang Department of Translational Medicine, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, 100850, Beijing, China aut NATIONALLICENCE 773 0- Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/16(2015-08-01), 6727-6735 0175-7598 99:16<6727 2015 99 253