Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Arch Biochem Biophys. 2011 Feb 15;506(2):223-35. doi: 10.1016/j.abb.2010.12.009. Epub 2010 Dec 13.
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-1β 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.
自噬是一种溶酶体降解途径，对生存、分化、发育和内稳态至关重要。越来越多的证据表明，自噬功能受损会导致多种疾病的发病机制。然而，自噬在肠道上皮中的作用尚不清楚，尽管先前的研究指出自噬与肠道炎症之间存在可能的关系。在这项研究中，我们研究了自噬在肠道上皮炎症反应中的作用。我们在肠道上皮细胞中生成了一种条件性缺失 Atg7 的小鼠，Atg7 是一种自噬调节基因。与对照小肠组织相比，LPS 诱导的 Atg7 缺陷型小肠上皮细胞 TNF-α 和 IL-1β mRNA 的产生增加。此外，LPS 诱导的 NF-κB 激活程度在 Atg7 缺陷型肠道上皮细胞中得到促进。这些结果表明，自噬可以减轻内毒素诱导的肠道上皮炎症反应，从而维持肠道内稳态。
