Caspse-11-GSDMD pathway is required for serum ferritin secretion in sepsis
Caspse-11-GSDMD pathway is required for serum ferritin secretion in sepsis
复制标题
Caspse-11-GSDMD 通路是脓毒症血清铁蛋白分泌所必需的
DOI：
10.1016/j.clim.2018.11.005
复制
发表时间：
2019-08-01
影响因子：
8.6
通讯作者：
Lu, Ben
中科院分区：
文献类型：
--
作者：
Wang, Dan;Yu, Songlin;Lu, Ben
铁蛋白是脊椎动物主要的铁储存分子，在许多情况下，包括炎症、神经退行性疾病和恶性疾病，都可以在血清中检测到铁蛋白。鉴于这一特点，血清铁蛋白经常被用作临床环境中的生物标志物。铁蛋白如何分泌到血清中引起了人们的广泛关注。虽然有研究发现正常情况下铁蛋白通过内质网（ER）高尔基体分泌途径或分泌溶酶体运输途径介导，但病理情况下，特别是脓毒症中铁蛋白的分泌途径并不是很清楚。在本报告中，我们采用小鼠脓毒症模型来研究脓毒症中铁蛋白的分泌途径。我们证明了caspase-11-GSDMD途径和相关的焦亡是体外和体内脓毒症中铁蛋白分泌所必需的。此外，我们的工作将焦亡与血清铁蛋白分泌联系起来，提出了铁蛋白的被动释放过程，增强了我们对铁蛋白分泌机制的理解。
Ferritin is the major iron storage molecule of vertebrates, which can be detected in serum under numerous conditions, including inflammatory, neurodegenerative, and malignant diseases. Given this character, serum ferritin is frequently used as a biomarker in clinical settings. How the ferritin secreted to the serum has attracted much attention. Although some studies have found ferritin was mediated via the endoplasmic reticulum (ER)Golgi secretion pathway or secretory lysosomes trafficking pathway under normal conditions, the secretion pathway of ferritin under pathological conditions, especially in sepsis is not very clear. In this report, we adopt a murine sepsis model to study the secretion pathway of ferritin in sepsis. We demonstrated caspase-11-GSDMD pathway and associated pyroptosis are required for secretion of ferritin in vitro and in vivo in sepsis. Moreover, our work connects pyroptosis to serum ferritin secretion and suggests a passive release process of ferritin, enhancing our understanding of the mechanism of ferritin secretion.