Core 1-derived mucin-type O-glycosylation protects against spontaneous gastritis and gastric cancer.

IF 9.8 2区计算机科学 Q1 COMPUTER SCIENCE, ARTIFICIAL INTELLIGENCE IEEE Transactions on Affective Computing Pub Date : 2020-01-06 DOI:10.1084/jem.20182325

Fei Liu, Jianxin Fu, Kirk Bergstrom, Xindi Shan, J Michael McDaniel, Samuel McGee, Xia Bai, Weichang Chen, Lijun Xia

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Abstract

Core 1-derived mucin-type O-glycans (O-glycans) are a major component of gastric mucus with an unclear role. To address this, we generated mice lacking gastric epithelial O-glycans (GEC C1galt1-/-). GEC C1galt1-/- mice exhibited spontaneous gastritis that progressed to adenocarcinoma with ∼80% penetrance by 1 yr. GEC C1galt1-/- gastric epithelium exhibited defective expression of a major mucus forming O-glycoprotein Muc5AC relative to WT controls, which was associated with impaired gastric acid homeostasis. Inflammation and tumorigenesis in GEC C1galt1-/- stomach were concurrent with activation of caspases 1 and 11 (Casp1/11)-dependent inflammasome. GEC C1galt1-/- mice genetically lacking Casp1/11 had reduced gastritis and gastric cancer progression. Notably, expression of Tn antigen, a truncated form of O-glycan, and CASP1 activation was associated with tumor progression in gastric cancer patients. These results reveal a critical role of O-glycosylation in gastric homeostasis and the protection of the gastric mucosa from Casp1-mediated gastric inflammation and cancer.

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源自核心 1 的粘蛋白型 O-糖基化可预防自发性胃炎和胃癌。

核心 1 衍生的粘蛋白型 O-聚糖（O-聚糖）是胃粘液的主要成分，其作用尚不明确。为了解决这个问题，我们培育了缺乏胃上皮 O 型糖的小鼠（GEC C1galt1-/-）。GEC C1galt1-/-小鼠表现出自发性胃炎，1年后发展为腺癌，其穿透率为80%。与 WT 对照组相比，GEC C1galt1-/- 胃上皮细胞表现出一种主要粘液形成 O 型糖蛋白 Muc5AC 的表达缺陷，这与胃酸平衡受损有关。GEC C1galt1-/-胃中的炎症和肿瘤发生与依赖于Caspase 1和11（Casp1/11）的炎性酶体的激活同时发生。基因缺失 Casp1/11 的 GEC C1galt1-/- 小鼠的胃炎和胃癌进展均有所减轻。值得注意的是，Tn 抗原（O-糖的一种截短形式）的表达和 CASP1 的激活与胃癌患者的肿瘤进展有关。这些结果揭示了 O-糖基化在胃稳态和保护胃黏膜免受 Casp1 介导的胃炎和胃癌影响中的关键作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

IEEE Transactions on Affective Computing COMPUTER SCIENCE, ARTIFICIAL INTELLIGENCE-COMPUTER SCIENCE, CYBERNETICS

CiteScore

15.00

自引率

6.20%

发文量

174

期刊介绍： The IEEE Transactions on Affective Computing is an international and interdisciplinary journal. Its primary goal is to share research findings on the development of systems capable of recognizing, interpreting, and simulating human emotions and related affective phenomena. The journal publishes original research on the underlying principles and theories that explain how and why affective factors shape human-technology interactions. It also focuses on how techniques for sensing and simulating affect can enhance our understanding of human emotions and processes. Additionally, the journal explores the design, implementation, and evaluation of systems that prioritize the consideration of affect in their usability. We also welcome surveys of existing work that provide new perspectives on the historical and future directions of this field.