Advances in IBD genetics

Limbergen, Johan Van; Radford‐Smith, Graham; Satsangi, Jack

doi:10.1038/nrgastro.2014.27

Cited by 121 publications

(76 citation statements)

References 208 publications

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“…Currently, the paradigm proposed is a feed-forward synergistic dysregulation of the mucosal epithelial barrier, the mucosal immune system, and gut microbiota (2,6,52). Metagenomic and genome-wide association studies have clearly confirmed the role of all three in the progression of IBD (12, 20, 24, 35, 46, 50a, 52).…”

mentioning

confidence: 98%

Activation of HIF-1α does not increase intestinal tumorigenesis

Xue¹,

Ramakrishnan²,

Shah

2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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The hypoxic response is mediated by two transcription factors, hypoxia-inducible factor (HIF)-1α and HIF-2α. These highly homologous transcription factors are induced in hypoxic foci and regulate cell metabolism, angiogenesis, cell proliferation, and cell survival. HIF-1α and HIF-2α are activated early in cancer progression and are important in several aspects of tumor biology. HIF-1α and HIF-2α have overlapping and distinct functions. In the intestine, activation of HIF-2α increases inflammation and colon carcinogenesis in mouse models. Interestingly, in ischemic and inflammatory diseases of the intestine, activation of HIF-1α is beneficial and can reduce intestinal inflammation. HIF-1α is a critical transcription factor regulating epithelial barrier function following inflammation. The beneficial value of pharmacological agents that chronically activate HIF-1α is decreased due to the tumorigenic potential of HIFs. The present study tested the hypothesis that chronic activation of HIF-1α may enhance colon tumorigenesis. Two models of colon cancer were assessed, a sporadic and a colitis-associated colon cancer model. Activation of HIF-1α in intestinal epithelial cells does not increase carcinogenesis or progression of colon cancer. Together, the data provide proof of principle that pharmacological activation of HIF-1α could be a safe therapeutic strategy for inflammatory bowel disease.

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confidence: 98%

Activation of HIF-1α does not increase intestinal tumorigenesis

Xue¹,

Ramakrishnan²,

Shah

2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Indeed, polymorphisms in multiple members of the NOD-like receptor family of intracellular pattern recognition receptors are associated with various inflammatory diseases (2,3). The NOD-like receptor family member NOD2 is one of best characterized genetic risk factors in the pathogenesis of Crohn disease (CD) 3 (4,5). NOD2, which is expressed in a variety of cell types, including intestinal epithelial cells, macrophages, and dendritic cells, functions as a sensor for bacterial peptidoglycan (6,7).…”

mentioning

confidence: 99%

A Genome-wide Small Interfering RNA (siRNA) Screen Reveals Nuclear Factor-κB (NF-κB)-independent Regulators of NOD2-induced Interleukin-8 (IL-8) Secretion

Warner

Burberry

Pliakas

et al. 2014

Journal of Biological Chemistry

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Background: Interleukin-8 (IL-8) is a potent proinflammatory cytokine. Results: We identify many regulators of IL-8 secretion induced by the pattern recognition receptor NOD2. Conclusion: Many diverse cellular processes, including protein ubiquitination and trafficking, specifically affect IL-8 secretion. Significance: The identified regulators, particularly those present in inflammatory disease loci, reveal molecular targets for therapeutic modulation of IL-8.

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“…A specific association of NKX2-3 rs1088365 with smoking CD patients has been observed (310 CD and 976 controls) (van der Heide et al, 2010). These studies have been reviewed (Cho and Brant, 2011;Van Limbergen et al, 2014).…”

Section: Inflammatory Bowel Disease (Ibd)mentioning

confidence: 99%