The Microbiota Protects against Ischemia/Reperfusion-Induced Intestinal Injury through Nucleotide-Binding Oligomerization Domain-Containing Protein 2 (NOD2) Signaling

Perez‐Chanona, Ernesto; Mühlbauer, Marcus; Jobin, Christian

doi:10.1016/j.ajpath.2014.07.014

Cited by 33 publications

(20 citation statements)

References 67 publications

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“…Diagram of the mechanisms of miR-29b-3p in controlling II/R damage. MiR-29b-3p decreased the expression levels of p-TAK1 and p65 via targeting TRAF3 to alleviate apoptosis and inflammation caused by II/R II/R injury-induced SIRS and MODS can lead to death in patients (L. Liu et al, 2018;Perez-Chanona, Mühlbauer, & Jobin, 2014;Rivers et al, 2001). As demonstrated in this study, II/R injury aggravated intestinal mucosa inflammation and apoptosis which can eventually cause SIRS and MODS.…”

Section: Figuresupporting

confidence: 53%

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MicroRNA‐29b‐3p reduces intestinal ischaemia/reperfusion injury via targeting of TNF receptor‐associated factor 3

Dai

Zhang

Han

et al. 2019

British J Pharmacology

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Background and Purpose The microRNA miR‐29b‐3p shows important roles in regulating apoptosis and inflammation. However, its effects on intestinal ischaemia/reperfusion (II/R) injury have not been reported. Here we have investigated the functions of miR‐29b‐3p on II/R injury on order to find drug targets to treat the injury. Experimental Approach Two models ‐ in vitro hypoxia/reoxygenation (H/R) of IEC‐6 cells; in vivo, II/R injury in C57BL/6 mice were used. Western blotting and dual‐luciferase reporter assays were used and mimic and siRNA transfection tests were applied to assess the effects of miR‐29b‐3p on II/R injury via targeting TNF receptor‐associated factor 3 (TRAF3). Key Results The H/R procedure decreased cell viability and promoted inflammation and apoptosis in IEC‐6 cells, and the II/R procedure also promoted intestinal inflammation and apoptosis in mice. Expression levels of miR‐29b‐3p were decreased in H/R‐induced cells and II/R‐induced intestinal tissues of mice compared with control group or sham group, which directly targeted TRAF3. Decreased miR‐29b‐3p level markedly increased TRAF3 expression via activating TGF‐α‐activated kinase 1 phosphorylation, increasing NF‐κB (p65) levels to promote inflammation, up‐regulating Bcl2‐associated X expression, and down‐regulating Bcl‐2 expression to trigger apoptosis. In addition, the miR‐29b‐3p mimetic and TRAF3 siRNA in IEC‐6 cells markedly suppressed apoptosis and inflammation to alleviate II/R injury via inhibiting TRAF3 signallimg. Conclusions and Implications The miR‐29b‐3p played a critical role in II/R injury, via targeting TRAF3, which should be considered as a significant drug target to treat the disease.

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Section: Figuresupporting

confidence: 53%

“…II/R injury‐induced SIRS and MODS can lead to death in patients (L. Liu et al, ; Perez‐Chanona, Mühlbauer, & Jobin, ; Rivers et al, ). As demonstrated in this study, II/R injury aggravated intestinal mucosa inflammation and apoptosis which can eventually cause SIRS and MODS.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐29b‐3p reduces intestinal ischaemia/reperfusion injury via targeting of TNF receptor‐associated factor 3

Dai

Zhang

Han

et al. 2019

British J Pharmacology

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“…While the aforementioned work supports a role for the intestinal microbiota in exacerbating I/R injury, results of recent studies indicated that conventionally derived mice with an intact commensal bacterial population exhibited less injury after intestinal or renal I/R when compared to that noted in germ-free mice (379, 632, 846, 847). The protection against intestinal I/R injury was abrogated in mice that were genetically deficient in nucleotide-binding oligomerization domain-containing protein 2 (Nod2), an intracellular pattern recognition receptor (PPR) that induces autophagy on detection of the microbial cell wall component, muramyl dipeptide (632).…”

Section: Gut Microbiome and I/rmentioning

confidence: 98%

“…The protection against intestinal I/R injury was abrogated in mice that were genetically deficient in nucleotide-binding oligomerization domain-containing protein 2 (Nod2), an intracellular pattern recognition receptor (PPR) that induces autophagy on detection of the microbial cell wall component, muramyl dipeptide (632). Treatment of Nod2 −/− with the autophagy inducer rapamycin protected against I/R injury.…”

Section: Gut Microbiome and I/rmentioning

confidence: 99%

Ischemia/Reperfusion

Kalogeris

Baines

Krenz

et al. 2016

Comprehensive Physiology

626

565

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Ischemic disorders, such as myocardial infarction, stroke, and peripheral vascular disease, are the most common causes of debilitating disease and death in westernized cultures. The extent of tissue injury relates directly to the extent of blood flow reduction and to the length of the ischemic period, which influence the levels to which cellular ATP and intracellular pH are reduced. By impairing ATPase-dependent ion transport, ischemia causes intracellular and mitochondrial calcium levels to increase (calcium overload). Cell volume regulatory mechanisms are also disrupted by the lack of ATP, which can induce lysis of organelle and plasma membranes. Reperfusion, although required to salvage oxygen-starved tissues, produces paradoxical tissue responses that fuel the production of reactive oxygen species (oxygen paradox), sequestration of proinflammatory immunocytes in ischemic tissues, endoplasmic reticulum stress, and development of postischemic capillary no-reflow, which amplify tissue injury. These pathologic events culminate in opening of mitochondrial permeability transition pores as a common end-effector of ischemia/reperfusion (I/R)-induced cell lysis and death. Emerging concepts include the influence of the intestinal microbiome, fetal programming, epigenetic changes, and microparticles in the pathogenesis of I/R. The overall goal of this review is to describe these and other mechanisms that contribute to I/R injury. Because so many different deleterious events participate in I/R, it is clear that therapeutic approaches will be effective only when multiple pathologic processes are targeted. In addition, the translational significance of I/R research will be enhanced by much wider use of animal models that incorporate the complicating effects of risk factors for cardiovascular disease.

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“…Inflammatory cytokines play an important role in the pathogenesis of ischemia–reperfusion induced injury . Increased production of IL‐6, TNF, IL‐1b and the neutrophil‐recruiting chemokine CXCL2 is associated with tissue damage during intestinal ischemia–reperfusion injury . Our results demonstrate that early induction of superoxide in the intestine at 1 h of ischemia precedes the induction of IL‐1b, CXCL2, and IL‐6 cytokines in ischemic intestine during reperfusion.…”

Section: Discussionmentioning

confidence: 95%

Europium‐Doped Cerium Oxide Nanoparticles Limit Reactive Oxygen Species Formation and Ameliorate Intestinal Ischemia–Reperfusion Injury

Gubernatorova

Liu

Othman

et al. 2017

Adv Healthcare Materials

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Accumulating evidence suggests that ischemia-reperfusion-induced injury is associated with the formation of reactive oxygen species (ROS). This study demonstrates the therapeutic effectiveness of novel europium-doped cerium oxide nanoparticles (Eu-doped Ceria NPs) as ROS scavengers in a mouse model of intestinal ischemia-reperfusion-induced injury. An increased production of superoxide radicals is detected in the intestine throughout the ischemia stage and again after initiating reperfusion. These changes in superoxide radical formation are associated with the induction of inflammatory cytokines in the intestine. This study further shows that Eu-Ceria NPs exhibit superoxide scavenging activity in vitro. Importantly, administration of Eu-Ceria NPs into the intestinal lumen during the onset of ischemia effectively blocks superoxide accumulation, reduces the expression of IL-1b, and ameliorates the intestinal pathology. These results suggest that early increased production of ROS during the ischemia-reperfusion promotes intestinal pathology and that mucosal delivery of Eu-Ceria NPs may be a potential therapeutic approach to block ROS accumulation and ameliorate the severity of intestinal disease.

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The Microbiota Protects against Ischemia/Reperfusion-Induced Intestinal Injury through Nucleotide-Binding Oligomerization Domain-Containing Protein 2 (NOD2) Signaling

Cited by 33 publications

References 67 publications

MicroRNA‐29b‐3p reduces intestinal ischaemia/reperfusion injury via targeting of TNF receptor‐associated factor 3

MicroRNA‐29b‐3p reduces intestinal ischaemia/reperfusion injury via targeting of TNF receptor‐associated factor 3

Ischemia/Reperfusion

Europium‐Doped Cerium Oxide Nanoparticles Limit Reactive Oxygen Species Formation and Ameliorate Intestinal Ischemia–Reperfusion Injury

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