Overexpression of the growth arrest and DNA damage–induced 45Α gene contributes to autoimmunity by promoting DNA demethylation in lupus T cells
dc.contributor.author | Li, Yaping | en_US |
dc.contributor.author | Zhao, Ming | en_US |
dc.contributor.author | Yin, Heng | en_US |
dc.contributor.author | Gao, Fei | en_US |
dc.contributor.author | Wu, Xiaoyan | en_US |
dc.contributor.author | Luo, Yongqi | en_US |
dc.contributor.author | Zhao, Sha | en_US |
dc.contributor.author | Zhang, Xiujuan | en_US |
dc.contributor.author | Su, Yuwen | en_US |
dc.contributor.author | Hu, Nan | en_US |
dc.contributor.author | Long, Hai | en_US |
dc.contributor.author | Richardson, Bruce C. | en_US |
dc.contributor.author | Lu, Qianjin | en_US |
dc.date.accessioned | 2010-06-02T19:49:22Z | |
dc.date.available | 2011-03-01T16:26:43Z | en_US |
dc.date.issued | 2010-05 | en_US |
dc.identifier.citation | Li, Yaping; Zhao, Ming; Yin, Heng; Gao, Fei; Wu, Xiaoyan; Luo, Yongqi; Zhao, Sha; Zhang, Xiujuan; Su, Yuwen; Hu, Nan; Long, Hai; Richardson, Bruce; Lu, Qianjin (2010). "Overexpression of the growth arrest and DNA damage–induced 45Α gene contributes to autoimmunity by promoting DNA demethylation in lupus T cells." Arthritis & Rheumatism 62(5): 1438-1447. <http://hdl.handle.net/2027.42/75771> | en_US |
dc.identifier.issn | 0004-3591 | en_US |
dc.identifier.issn | 1529-0131 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/75771 | |
dc.description.abstract | Objective Demethylation of CD11a and CD70 regulatory regions in CD4+ T cells contributes to the development of autoreactivity and overstimulation of autoantibodies. Because growth arrest and DNA damage–induced 45Α (GADD45Α) reduces epigenetic silencing of genes by removing methylation marks, this study examined whether the gadd45A gene could contribute to autoimmunity by promoting DNA demethylation in T cells from patients with systemic lupus erythematosus (SLE). Methods Levels of GADD45Α, CD11a, and CD70 messenger RNA (mRNA) and protein were detected by real-time reverse transcription–polymerase chain reaction and Western blotting or flow cytometry. Global DNA methylation was evaluated using Methylamp global DNA methylation quantification kits. Detection of CD4+ T cell proliferation and autologous B cell IgG antibodies was performed using commercially available kits. CD11a and CD70 promoter methylation was determined with bisulfite sequencing. Results Elevated gadd45A mRNA expression and global DNA hypomethylation were observed in CD4+ T cells from SLE patients. The levels of gadd45A mRNA were inversely proportional to the levels of DNA methylation. Positive correlations were found between gadd45A and CD11a/CD70 mRNA levels. Expression of gadd45A mRNA was increased in CD4+ T cells following ultraviolet B irradiation, and this was accompanied by increased levels of CD11a and CD70 mRNA. Moreover, increased expression of gadd45A , CD11a, and CD70 mRNA was accompanied by increased autoreactivity and excessive B cell stimulation in gadd45A -transfected CD4+ T cells. CD11a promoter methylation was also significantly reduced in transfected cells. Transfection of gadd45A small interfering RNA inhibited the autoreactivity of SLE CD4+ T cells and led to significant increases in the methylation levels of the CD11a and CD70 promoter regions. Conclusion These findings indicate that gadd45A may contribute to lupus-like autoimmunity by promoting DNA demethylation in SLE CD4+ T cells. | en_US |
dc.format.extent | 329931 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.title | Overexpression of the growth arrest and DNA damage–induced 45Α gene contributes to autoimmunity by promoting DNA demethylation in lupus T cells | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Geriatrics | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | University of Michigan and Ann Arbor VA Medical Center, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationother | Second Xiangya Hospital and Central South University, Changsha, China | en_US |
dc.contributor.affiliationother | Second Xiangya Hospital and Central South University, Changsha, China | en_US |
dc.contributor.affiliationother | Second Xiangya Hospital and Central South University, Changsha, China | en_US |
dc.contributor.affiliationother | Second Xiangya Hospital and Central South University, Changsha, China | en_US |
dc.contributor.affiliationother | Second Xiangya Hospital and Central South University, Changsha, China | en_US |
dc.contributor.affiliationother | Second Xiangya Hospital and Central South University, Changsha, China | en_US |
dc.contributor.affiliationother | Second Xiangya Hospital and Central South University, Changsha, China | en_US |
dc.contributor.affiliationother | Second Xiangya Hospital and Central South University, Changsha, China | en_US |
dc.contributor.affiliationother | Second Xiangya Hospital and Central South University, Changsha, China | en_US |
dc.contributor.affiliationother | Second Xiangya Hospital and Central South University, Changsha, China | en_US |
dc.contributor.affiliationother | Second Xiangya Hospital and Central South University, Changsha, China | en_US |
dc.contributor.affiliationother | Second Xiangya Hospital and Central South University, Changsha, China ; Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, Hunan 410011, China | en_US |
dc.identifier.pmid | 20131288 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/75771/1/27363_ftp.pdf | |
dc.identifier.doi | 10.1002/art.27363 | en_US |
dc.identifier.source | Arthritis & Rheumatism | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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