The unfolded protein response and gastrointestinal disease.
Semin Immunopathol
; 35(3): 307-19, 2013 May.
Article
em En
| MEDLINE
| ID: mdl-23588234
ABSTRACT
As the inner lining of the gastrointestinal tract, the intestinal epithelium serves an essential role in innate immune function at the interface between the host and microbiota. Given the unique environmental challenges and thus physiologic secretory functions of this surface, it is exquisitely sensitive to perturbations that affect its capacity to resolve endoplasmic reticulum (ER) stress. Genetic deletion of factors involved in the unfolded protein response (UPR), which functions in the resolution of ER stress that arises from misfolded proteins, result in spontaneous intestinal inflammation closely mimicking human inflammatory bowel disease (IBD). This is demonstrated by observations wherein deletion of genes such as Xbp1 and Agr2 profoundly affects the intestinal epithelium and results in spontaneous intestinal inflammation. Moreover, both genes, along with others (e.g., ORDML3) represent genetic risk factors for human IBD, both Crohn's disease and ulcerative colitis. Here, we review the current mechanistic understanding for how unresolved ER stress can lead to intestinal inflammation and highlight the findings that implicate ER stress as a genetically affected biological pathway in IBD. We further discuss environmental and microbial factors that might impact on the epithelium's capacity to resolve ER stress and which may constitute exogenous factors that may precipitate disease in genetically susceptible individuals.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Resposta a Proteínas não Dobradas
/
Gastroenteropatias
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Semin Immunopathol
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
PATOLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Reino Unido