Autophagy and Crohn's Disease: At the Crossroads of Infection, Inflammation, Immunity, and Cancer

被引：62

作者：

Brest, P. ^{[1
]}

Corcelle, E. A. ^{[2
,3
]}

Cesaro, A. ^{[1
]}

Chargui, A. ^{[1
]}

Belaid, A. ^{[1
]}

Klionsky, D. J. ^{[4
]}

Vouret-Craviari, V. ^{[1
]}

Hebuterne, X. ^{[1
,5
]}

Hofman, P. ^{[1
,6
]}

Mograbi, B. ^{[1
]}

机构：

[1] Univ Nice Sophia Antipolis, Fac Med, INSERM, ERI 21,EA 4319, Nice, France

[2] Danish Canc Soc, Inst Canc Biol, Apoptosis Dept, Copenhagen, Denmark

[3] Danish Canc Soc, Inst Canc Biol, Ctr Genotox Stress Res, Copenhagen, Denmark

[4] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA

[5] Hop Archet II, Ctr Hosp Univ Nice, Nice, France

[6] Pasteur Hosp, Lab Clin & Expt Pathol, Nice, France

来源：

CURRENT MOLECULAR MEDICINE | 2010年 / 10卷 / 05期

关键词：

Autophagy; Crohn's disease; infection; inflammation; immunity; cancer; GENOME-WIDE ASSOCIATION; INDUCIBLY EXPRESSED GTPASE; BOWEL-DISEASE; SUSCEPTIBILITY LOCI; FRAMESHIFT MUTATION; RESISTANCE GTPASES; TOXOPLASMA-GONDII; CELLULAR-RESPONSE; GENETIC-VARIANTS; APOPTOTIC CELLS;

D O I：

10.2174/156652410791608252

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Inflammatory bowel diseases (IBD) are common inflammatory disorders of the gastrointestinal tract that include ulcerative colitis (UC) and Crohn's disease (CD). The incidences of IBD are high in North America and Europe, affecting as many as one in 500 people. These diseases are associated with high morbidity and mortality. Colorectal cancer risk is also increased in IBD, correlating with inflammation severity and duration. IBD are now recognized as complex multigenetic disorders involving at least 32 different risk loci. In 2007, two different autophagy-related genes, ATG16L1 (autophagy-related gene 16-like 1) and IRGM (immunity-related GTPase M) were shown to be specifically involved in CD susceptibility by three independent genome-wide association studies. Soon afterwards, more than forty studies confirmed the involvement of ATG16L1 and IRGM variants in CD susceptibility and gave new information on the importance of macroautophagy (hereafter referred to as autophagy) in the control of infection, inflammation, immunity and cancer. In this review, we discuss how such findings have undoubtedly changed our understanding of CD pathogenesis. A unifying autophagy model then emerges that may help in understanding the development of CD from bacterial infection, to inflammation and finally cancer. The Pandora's box is now open, releasing a wave of hope for new therapeutic strategies in treating Crohn's disease.

引用

页码：486 / 502

页数：17

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