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Arch Biochem Biophys ; 506(2): 223-35, 2011 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-21156154

RESUMO

Autophagy is a lysosomal degradation pathway that is essential for survival, differentiation, development and homeostasis. There is growing evidence that impaired autophagy leads to the pathogenesis of diverse diseases. However, the role of autophagy in intestinal epithelium is not clearly understood, although previous studies have pointed out the possibility for the relationships of autophagy with bowel inflammation. In this study, we investigated the involvement of autophagy in intestinal epithelium with inflammatory responses. We generated the mice with a conditional deletion of Atg7, which is one of the autophagy regulated gene, in intestinal epithelium. In Atg7-deficient small intestinal epithelium, LPS-induced production of TNF-α and IL-1ß mRNA was enhanced in comparison to the control small intestinal tissues. In addition, the degree of LPS-induced activation of NF-κB was promoted in Atg7-deficient intestinal epithelium. These results demonstrate that autophagy can attenuate endotoxin-induced inflammatory responses in intestinal epithelium resulting in the maintenance of intestinal homeostasis.


Assuntos
Autofagia/fisiologia , Inflamação/patologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Lipopolissacarídeos/toxicidade , NF-kappa B/metabolismo , Animais , Autofagia/efeitos dos fármacos , Autofagia/genética , Proteína 7 Relacionada à Autofagia , Sequência de Bases , DNA/metabolismo , Primers do DNA/genética , Inflamação/genética , Inflamação/metabolismo , Inflamação/prevenção & controle , Interleucina-1beta/genética , Mucosa Intestinal/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Proteínas Associadas aos Microtúbulos/deficiência , Proteínas Associadas aos Microtúbulos/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/genética
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