Epigenetics in the pathogenesis of systemic lupus erythematosus

被引:27
作者
Altorok, Nezam [1 ]
Sawalha, Amr H. [1 ]
机构
[1] Univ Michigan, Dept Internal Med, Div Rheumatol, Ann Arbor, MI 48109 USA
关键词
DNA methylation; epigenetics; histone modification; lupus; microRNA; CD4(+) T-CELLS; DNA METHYLATION; GENE-EXPRESSION; PROTEIN; PROMOTER; OVEREXPRESSION; DEMETHYLATION; CONTRIBUTES; MECP2; METHYLTRANSFERASE;
D O I
10.1097/BOR.0b013e328364206f
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
Purpose of review There has been a tremendous interest to understand the mechanisms that regulate gene expression in autoimmunity and their effect on disease phenotypes by exploring different epigenetic mechanisms. In this review, we will introduce lupus epigenetics through reviewing historical key findings, then we will focus on the most recent and relevant findings in this field reflecting our own and naturally biased opinion. Recent findings In addition to uncovering more methylation-sensitive loci in critical genes and proposing a role for these genes in the pathogenesis of lupus, there has been a great interest in high-resolution unbiased genome-wide epigenetic studies to investigate aberrant methylation and histone code patterns, the two major epigenetic markers. In recent years, we have also witnessed an increasing interest in the role of microRNAs in the pathogenesis of lupus, and as candidate molecules with intriguing therapeutic potentials. Summary Epigenetics is an exciting field that is serving as a link, as we currently understand, between genetic susceptibility and the environment in predisposing to lupus. Certainly, epigenetic aberrancies play a fundamental role in propagation of the lupus phenotype. Whether the available epigenetic-modifying agents would be useful treating human lupus is still an open question, but is unlikely in our opinion. Indeed, gene-specific epigenetic modifiers will be a challenging and an exciting area for future research.
引用
收藏
页码:569 / 576
页数:8
相关论文
共 64 条
[1]
The epigenetic face of systemic lupus erythematosus [J].
Ballestar, E ;
Esteller, M ;
Richardson, BC .
JOURNAL OF IMMUNOLOGY, 2006, 176 (12) :7143-7147
[2]
Defective activity of ERK-1 and ERK-2 mitogen-activated protein kinases in peripheral blood T lymphocytes from patients with systemic lupus erythematosus:: potential role of altered coupling of Ras guanine nucleotide exchange factor hSos to adapter protein Grb2 in lupus T cells [J].
Cedeño, S ;
Cifarelli, DF ;
Blasini, AM ;
Paris, M ;
Placeres, F ;
Alonso, G ;
Rodriguez, MA .
CLINICAL IMMUNOLOGY, 2003, 106 (01) :41-49
[3]
MeCP2, a key contributor to neurological disease, activates and represses transcription [J].
Chahrour, Maria ;
Jung, Sung Yun ;
Shaw, Chad ;
Zhou, Xiaobo ;
Wong, Stephen T. C. ;
Qin, Jun ;
Zoghbi, Huda Y. .
SCIENCE, 2008, 320 (5880) :1224-1229
[4]
Induction of PP2A Bβ, a regulator of IL-2 deprivation-induced T-cell apoptosis, is deficient in systemic lupus erythematosus [J].
Crispin, Jose C. ;
Apostolidis, Sokratis A. ;
Finnell, Melissa I. ;
Tsokos, George C. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (30) :12443-12448
[5]
Identification of a Common Lupus Disease-Associated microRNA Expression Pattern in Three Different Murine Models of Lupus [J].
Dai, Rujuan ;
Zhang, Yan ;
Khan, Deena ;
Heid, Bettina ;
Caudell, David ;
Crasta, Oswald ;
Ahmed, S. Ansar .
PLOS ONE, 2010, 5 (12) :1-8
[6]
DEAPEN D, 1992, ARTHRITIS RHEUM, V35, P311
[7]
Hydralazine may induce autoimmunity by inhibiting extracellular signal-regulated kinase pathway signaling [J].
Deng, C ;
Lu, QJ ;
Zhang, ZY ;
Rao, T ;
Attwood, J ;
Yung, R ;
Richardson, B .
ARTHRITIS AND RHEUMATISM, 2003, 48 (03) :746-756
[8]
Deng C, 2001, ARTHRITIS RHEUM, V44, P397, DOI 10.1002/1529-0131(200102)44:2<397::AID-ANR59>3.0.CO
[9]
2-N
[10]
Decreased MicroRNA-142-3p/5p Expression Causes CD4+T Cell Activation and B Cell Hyperstimulation in Systemic Lupus Erythematosus [J].
Ding, Shu ;
Liang, Yunsheng ;
Zhao, Ming ;
Liang, Gongping ;
Long, Hai ;
Zhao, Sha ;
Wang, Yu ;
Yin, Heng ;
Zhang, Peng ;
Zhang, Qing ;
Lu, Qianjin .
ARTHRITIS AND RHEUMATISM, 2012, 64 (09) :2953-2963