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Intra-articular lentivirus-mediated delivery of galectin-3 shRNA and galectin-1 gene ameliorates collagen-induced arthritis

Gene Therapy volume 17, pages 1225–1233 (2010)Cite this article

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Abstract

Different members of the galectin family may have inhibitory or stimulatory roles in controlling immune responses and regulating inflammatory reactions in autoimmune diseases such as rheumatoid arthritis (RA). A hypothetical model of a cross talk between galectin-1 and galectin-3 has been established in the circumstance of rheumatoid joints. As galectin-3 is a positive regulator and galectin-1 is a negative regulator of inflammation and autoimmune responses, in this study we evaluated the effects of local knockdown of galectin-3 or overexpression of galectin-1 on ameliorating collagen-induced arthritis (CIA) in rats. Lentiviral vectors encoding galectin-3 small hairpin RNA (shRNA) and galectin-1, as well as two control vectors expressing luciferase shRNA and green fluorescent protein, were individually injected intra-articularly into the ankle joints of rats with CIA, and their treatment responses were monitored by measuring the clinical, radiological and histological changes. Our results show that both knockdown of galectin-3 and overexpression of galectin-1 induced higher percentages of antigen-induced T-cell death in the lymph node cells from arthritic rats. Furthermore, these treatments significantly reduced articular index scores, radiographic scores and histological scores, accompanied with decreased T-cell infiltrates and reduced microvessel density in the ankle joints. Our findings implicate galectin-3 and galectin-1 as potential therapeutic targets for the treatment of RA.

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Acknowledgements

We thank Dr D Trono (Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland) for generously providing pWPT, pWPXL, pLVTHM, psPAX2 and pMD2G plasmids for lentivirus production. We also thank Dr LJ Chang (Department of Molecular Genetics and Microbiology, University of Florida) for providing TE671 cells. This work was supported by grants from the Department of Health, Executive Yuan (DOH96-TD-I-111-TM014 and DOH97-TD-I-111-TM015), National Science Council (NSC96-2314-B-006-002 and NSC98-2628-B-006-014-MY3), and National Cheng Kung University Landmark Project (NCKU-97-R10), Taiwan.

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  1. C-R Wang and A-L Shiau: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Internal Medicine, Section of Rheumatology and Immunology, National Cheng Kung University Medical College, Tainan, Taiwan

    C-R Wang

  2. Department of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan, Taiwan

    C-R Wang, A-L Shiau, Z-S Cheng, C-H Lee, Y-T Yo, C-W Lo, Y-S Lin & H-Y Juan

  3. Department of Biochemistry and Molecular Biology, National Cheng Kung University Medical College, Tainan, Taiwan

    S-Y Chen, Y-T Li & C-L Wu

  4. Institute of Oral Medicine, National Cheng Kung University Medical College, Tainan, Taiwan

    Y-L Chen

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Wang, CR., Shiau, AL., Chen, SY. et al. Intra-articular lentivirus-mediated delivery of galectin-3 shRNA and galectin-1 gene ameliorates collagen-induced arthritis. Gene Ther 17, 1225–1233 (2010). https://doi.org/10.1038/gt.2010.78

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