Released Mitochondrial DNA Following Intestinal Ischemia Reperfusion Induces the Inflammatory Response and Gut Barrier Dysfunction

Abstract Ischemia-reperfusion (I/R) injury is a challenging clinical problem, especially injuries involving the gastrointestinal tract. Mitochondrial DNA (mtDNA) is released upon cell death and stress, and can induce the inflammatory response. We aimed to investigate the role of mtDNA in the pathoge...

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Autores principales:	Qiongyuan Hu, Huajian Ren, Jianan Ren, Qinjie Liu, Jie Wu, Xiuwen Wu, Guanwei Li, Gefei Wang, Guosheng Gu, Kun Guo, Zhiwu Hong, Song Liu, Jieshou Li
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/17f5655cf2ef41399ea319ea2c83f0ef
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spelling	oai:doaj.org-article:17f5655cf2ef41399ea319ea2c83f0ef2021-12-02T11:41:13ZReleased Mitochondrial DNA Following Intestinal Ischemia Reperfusion Induces the Inflammatory Response and Gut Barrier Dysfunction10.1038/s41598-018-25387-82045-2322https://doaj.org/article/17f5655cf2ef41399ea319ea2c83f0ef2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25387-8https://doaj.org/toc/2045-2322Abstract Ischemia-reperfusion (I/R) injury is a challenging clinical problem, especially injuries involving the gastrointestinal tract. Mitochondrial DNA (mtDNA) is released upon cell death and stress, and can induce the inflammatory response. We aimed to investigate the role of mtDNA in the pathogenesis of intestinal I/R. Intestinal I/R model was established with clamping of the superior mesenteric artery, and IEC-6 cells were incubated under hypoxia/reoxygenation (H/R) conditions to simulate I/R injury. Using in vitro models, H/R up-regulated oxidative stress, disrupted mitochondrial activity and the mitochondrial membrane potential, induced apoptosis and elevated the mtDNA levels in the supernatant of intestinal epithelial cells, and the co-culture of mtDNA with human primary dendritic cells significantly elevated TLR9-MyD88 expression and enhanced the production of inflammatory cytokines and chemokines. MtDNA was also released in a mouse model of intestinal I/R and was associated with the increased secretion of inflammatory cytokines and increased gut barrier injury compared with that of the sham group. We concluded that mtDNA contributes to I/R injury and may serve as a biomarker of intestinal I/R. We further suggest that oxidized mtDNA originated from IECs during intestinal I/R exacerbates the acute proinflammatory process by eliciting the production of proinflammatory cytokines and chemokines.Qiongyuan HuHuajian RenJianan RenQinjie LiuJie WuXiuwen WuGuanwei LiGefei WangGuosheng GuKun GuoZhiwu HongSong LiuJieshou LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Qiongyuan Hu Huajian Ren Jianan Ren Qinjie Liu Jie Wu Xiuwen Wu Guanwei Li Gefei Wang Guosheng Gu Kun Guo Zhiwu Hong Song Liu Jieshou Li Released Mitochondrial DNA Following Intestinal Ischemia Reperfusion Induces the Inflammatory Response and Gut Barrier Dysfunction
description	Abstract Ischemia-reperfusion (I/R) injury is a challenging clinical problem, especially injuries involving the gastrointestinal tract. Mitochondrial DNA (mtDNA) is released upon cell death and stress, and can induce the inflammatory response. We aimed to investigate the role of mtDNA in the pathogenesis of intestinal I/R. Intestinal I/R model was established with clamping of the superior mesenteric artery, and IEC-6 cells were incubated under hypoxia/reoxygenation (H/R) conditions to simulate I/R injury. Using in vitro models, H/R up-regulated oxidative stress, disrupted mitochondrial activity and the mitochondrial membrane potential, induced apoptosis and elevated the mtDNA levels in the supernatant of intestinal epithelial cells, and the co-culture of mtDNA with human primary dendritic cells significantly elevated TLR9-MyD88 expression and enhanced the production of inflammatory cytokines and chemokines. MtDNA was also released in a mouse model of intestinal I/R and was associated with the increased secretion of inflammatory cytokines and increased gut barrier injury compared with that of the sham group. We concluded that mtDNA contributes to I/R injury and may serve as a biomarker of intestinal I/R. We further suggest that oxidized mtDNA originated from IECs during intestinal I/R exacerbates the acute proinflammatory process by eliciting the production of proinflammatory cytokines and chemokines.
format	article
author	Qiongyuan Hu Huajian Ren Jianan Ren Qinjie Liu Jie Wu Xiuwen Wu Guanwei Li Gefei Wang Guosheng Gu Kun Guo Zhiwu Hong Song Liu Jieshou Li
author_facet	Qiongyuan Hu Huajian Ren Jianan Ren Qinjie Liu Jie Wu Xiuwen Wu Guanwei Li Gefei Wang Guosheng Gu Kun Guo Zhiwu Hong Song Liu Jieshou Li
author_sort	Qiongyuan Hu
title	Released Mitochondrial DNA Following Intestinal Ischemia Reperfusion Induces the Inflammatory Response and Gut Barrier Dysfunction
title_short	Released Mitochondrial DNA Following Intestinal Ischemia Reperfusion Induces the Inflammatory Response and Gut Barrier Dysfunction
title_full	Released Mitochondrial DNA Following Intestinal Ischemia Reperfusion Induces the Inflammatory Response and Gut Barrier Dysfunction
title_fullStr	Released Mitochondrial DNA Following Intestinal Ischemia Reperfusion Induces the Inflammatory Response and Gut Barrier Dysfunction
title_full_unstemmed	Released Mitochondrial DNA Following Intestinal Ischemia Reperfusion Induces the Inflammatory Response and Gut Barrier Dysfunction
title_sort	released mitochondrial dna following intestinal ischemia reperfusion induces the inflammatory response and gut barrier dysfunction
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/17f5655cf2ef41399ea319ea2c83f0ef
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Released Mitochondrial DNA Following Intestinal Ischemia Reperfusion Induces the Inflammatory Response and Gut Barrier Dysfunction

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