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GSDMB不依赖于焦亡来调节上皮的修复
作者:小柯机器人 发布时间:2022/1/16 13:10:00

美国凯斯西储大学医学院Theresa T. Pizarro研究团队发现,GSDMB不依赖于焦亡来调节上皮的修复。2022年1月11日,《细胞》杂志在线发表了这项成果。

研究人员报告了在炎症性肠病中Gasdermin B(GSDMB)的增加,并且单细胞分析确定了上皮细胞对炎症性结肠细胞/隐窝顶结肠细胞的特异性。令人惊讶的是,机理实验和转录组分析显示,在激活的上皮细胞和类器官中缺乏固有的GSDMB依赖性焦亡,而是指出在体外伤口闭合过程中增殖和迁移,这在GSDMB缺陷的细胞中停止,并显示出超粘性和依赖PDGF-A介导FAK磷酸化的局部粘连增强。重要的是,携带疾病相关的GSDMB SNP会导致功能缺陷,破坏上皮细胞的恢复/修复,这就确定了GSDMB是恢复上皮屏障功能和解决炎症的关键因素。

据了解,Gasdermin是一个结构相关的蛋白质家族,最初是由于其在焦亡中的作用而被描述。GSDMB是目前研究最少的,虽然它与慢性粘膜炎症的遗传易感性有很好的关系,但对其在活跃疾病状态下的功能相关性知之甚少。

附:英文原文

Title: GSDMB is increased in IBD and regulates epithelial restitution/repair independent of pyroptosis

Author: Nitish Rana, Giuseppe Privitera, Hannah C. Kondolf, Katarzyna Bulek, Susana Lechuga, Carlo De Salvo, Daniele Corridoni, Agne Antanaviciute, Rebecca L. Maywald, Alexander M. Hurtado, Junjie Zhao, Emina H. Huang, Xiaoxia Li, E. Ricky Chan, Alison Simmons, Giorgos Bamias, Derek W. Abbott, Jason D. Heaney, Andrei I. Ivanov, Theresa T. Pizarro

Issue&Volume: 2022-01-11

Abstract: Gasdermins are a family of structurally related proteins originally described fortheir role in pyroptosis. Gasdermin B (GSDMB) is currently the least studied, andwhile its association with genetic susceptibility to chronic mucosal inflammatorydisorders is well established, little is known about its functional relevance duringactive disease states. Herein, we report increased GSDMB in inflammatory bowel disease,with single-cell analysis identifying epithelial specificity to inflamed colonocytes/crypttop colonocytes. Surprisingly, mechanistic experiments and transcriptome profilingreveal lack of inherent GSDMB-dependent pyroptosis in activated epithelial cells andorganoids but instead point to increased proliferation and migration during in vitro wound closure, which arrests in GSDMB-deficient cells that display hyper-adhesivenessand enhanced formation of vinculin-based focal adhesions dependent on PDGF-A-mediatedFAK phosphorylation. Importantly, carriage of disease-associated GSDMB SNPs confers functional defects, disrupting epithelial restitution/repair, which,altogether, establishes GSDMB as a critical factor for restoration of epithelial barrierfunction and the resolution of inflammation.

DOI: 10.1016/j.cell.2021.12.024

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)01487-2

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/