Pancreatic glycoprotein 2 is a first line of defense for mucosal protection in intestinal inflammation.

Pancreatic glycoprotein 2 is a first line of defense for mucosal protection in intestinal inflammation.
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胰腺糖蛋白2是肠道炎症中粘膜保护的第一道防线。

DOI:
10.1038/s41467-021-21277-2
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发表时间:
2021-02-16
影响因子:
16.6
通讯作者:
Kiyono H
Kiyono H
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kurashima Y;Kigoshi T;Murasaki S;Arai F;Shimada K;Seki N;Kim YG;Hase K;Ohno H;Kawano K;Ashida H;Suzuki T;Morimoto M;Saito Y;Sasou A;Goda Y;Yuki Y;Inagaki Y;Iijima H;Suda W;Hattori M;Kiyono H

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黏附性和侵袭性共生细菌(如大肠杆菌)的增加以及随后对上皮屏障的破坏与炎症性肠病(IBD)的发病机制有关。然而,对这种屏障破坏的保护系统还没有完全了解。在这里,我们发现胰腺腺泡细胞分泌的腔内糖蛋白2 (GP2)在化学诱导的结肠炎小鼠中以tnf依赖的方式诱导。克罗恩病患者粪便GP2浓度也升高。此外,与完整小鼠相比,胰腺特异性GP2缺陷结肠炎小鼠具有更严重的肠道炎症和更大的粘膜大肠杆菌群,这表明消化道GP2结合共生大肠杆菌,阻止上皮附着和渗透。因此,胰肠屏障轴和胰腺GP2在肠道炎症期间作为抵抗粘附性和侵袭性共生菌的第一道防线是重要的。糖蛋白-2 (GP-2)可以保护肠上皮屏障免受细菌侵害,并与预防克罗恩病有关。在这里,作者表明胰腺GP-2是肠腔GP-2的来源,它结合细菌并阻止它们附着在上皮上,也限制了DSS结肠炎小鼠模型的病理。
Increases in adhesive and invasive commensal bacteria, such as Escherichia coli, and subsequent disruption of the epithelial barrier is implicated in the pathogenesis of inflammatory bowel disease (IBD). However, the protective systems against such barrier disruption are not fully understood. Here, we show that secretion of luminal glycoprotein 2 (GP2) from pancreatic acinar cells is induced in a TNF–dependent manner in mice with chemically induced colitis. Fecal GP2 concentration is also increased in Crohn’s diease patients. Furthermore, pancreas-specific GP2-deficient colitis mice have more severe intestinal inflammation and a larger mucosal E. coli population than do intact mice, indicating that digestive-tract GP2 binds commensal E. coli, preventing epithelial attachment and penetration. Thus, the pancreas–intestinal barrier axis and pancreatic GP2 are important as a first line of defense against adhesive and invasive commensal bacteria during intestinal inflammation. Glycoprotein-2 (GP-2) can protect the intestinal epithelial barrier from bacteria and is associated with protection against Crohn’s disease. Here, the authors show pancreatic GP-2 is the source of the intestine’s luminal GP-2 that binds bacteria and prevents them from attaching to the epithelium, also limiting pathology in a DSS colitis mouse model.
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