MiR‐146a protects small intestine against ischemia/reperfusion injury by down‐regulating TLR4/TRAF6/NF‐κB pathway

He, Xuemei; Zheng, Ying-Qiang; Liu, Shengzhi; Shi, Sen; Liu, Yong; He, Yanzheng; Zhang, Chunxiang; Zhou, Xiangyu

doi:10.1002/jcp.26124

Cited by 69 publications

(47 citation statements)

References 32 publications

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“…MicroRNAs (miRNAs) are important endogenous regulators leading to RNA degradation and/or inhibition of protein synthesis (He et al, ; Y. Hu et al, ; Z. Liu et al, ). Recent studies have shown that some miRNAs including miR‐378, miR‐351‐5P, and miR‐665‐3p play important roles in regulating II/R injury (Y. Hu et al, ; Z. Li et al, ; Y. Li, Wen, et al, ; Y. Li, Xu, et al, ).…”

Section: Introductionmentioning

confidence: 99%

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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: Introductionmentioning

confidence: 99%

“…MicroRNAs (miRNAs) are important endogenous regulators leading to RNA degradation and/or inhibition of protein synthesis (He et al, 2018;Y. Hu et al, 2018;Z.…”

Section: Introductionmentioning

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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“…40 MicroRNA-146a was also suppressed 15-fold in the LCHS/CS group compared with LCHS/CSþBB and naïve rodents. He and colleagues 41 found decreased expression of miR-146a in patients with small intestine ischemia and ischemia reperfusion injury, and determined that improved intestine epithelial cell survival occurs with inhibition of Toll-like receptor 4 and tumor necrosis factor receptor-associated factor-6, leading to decreased nuclear factor kappa light chain enhancer of activated B cells, which has been shown to play a role in early erythroid proliferation and suppression of erythroid specific genes. 42 These miR findings correlate with our previous studies demonstrating significant erythroid growth suppression after LCHS/CS and improvement in inflammation and erythropoiesis with the use of propranolol after LCHS/CS.…”

Section: Discussionmentioning

confidence: 99%

Effect of Beta-Blockade on the Expression of Regulatory MicroRNA after Severe Trauma and Chronic Stress

Miller

Loftus

Kannan

et al. 2020

Journal of the American College of Surgeons

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BACKGROUND: Beta-blockade administration after lung contusion, hemorrhagic shock, and chronic stress has been shown to improve bone marrow function, decrease hypercatecholaminemia, and reduce inflammation. MicroRNAs (miR) are critical biologic regulators that can downregulate gene expression by causing messenger RNA degradation or inhibition of translation. This study sought to expand our understanding of the molecular mechanisms underlying the reduced inflammatory response after the administration of beta-blockade (BB) in our rodent trauma model. STUDY DESIGN: Male Sprague-Dawley rats aged 8 to 9 weeks were randomized to lung contusion, hemorrhagic shock with daily restraint stress (LCHS/CS) or LCHS/CS plus propranolol (LCHS/ CSþBB). Restraint stress occurred 2 hours daily after LCHS. Propranolol (10 mg/kg) was given daily until day 7. Total RNA and miR were isolated from bone marrow and genomewide miR expression patterns were assayed. Bone marrow cytokine expression was determined with quantitative polymerase chain reaction. RESULTS: LCHS/CS led to significantly increased bone marrow expression of interleukin (IL) 1b, tumor necrosis factor-a, IL-6, nitric oxide, and plasma C-reactive protein. There were marked differences in expression of 45 miRs in the LCHS/CSþBB group compared with the LCHS/CS group when using a p value <0.001. Rno-miR-27a and miR-25 were upregulated 7-to 8-fold in the rodents who underwent LCHS/CSþBB compared with LCHS/CS alone, and this correlated with reduced bone marrow expression of IL-1b, tumor necrosis factor-a, IL-6, nitric oxide, and reduced plasma C-reactive protein in the LCHS/CSþBB group. CONCLUSIONS: The genomic and miR expression patterns in bone marrow after LCHS/CS differed significantly compared with rodents that received propranolol after LCHS/CS. The use of BB after severe trauma can help mitigate persistent inflammation by upregulating Rno-miR-27a and miR-25 and reducing inflammatory cytokines in those who remain critically ill.

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“…TnF receptor-associated factor (TraF) is an important linker molecule in the TnF superfamily; TRAF6 is involved in inflammation and immune responses by mediating inflammatory and apoptotic signaling pathways (15). in addition, TraF may serve a key role by activating the nF-κB signaling pathway (16)(17)(18)(19)(20)(21)(22)(23). a previous study reported that BaFF activates B cells through the nF-κB signaling pathway to secrete excess iga1, which leads to iga nephropathy-like alterations in mouse kidneys (14).…”

Section: Introductionmentioning

confidence: 98%

BAFF is involved in the pathogenesis of IgA nephropathy by activating the TRAF6/NF‑κB signaling pathway in glomerular mesangial cells

Cao

Chen

et al. 2019

Mol Med Report

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The aim of the present study was to investigate the involvement of B cell-activating factor (BaFF) in the pathogenesis of iga nephropathy by activating the tumor necrosis factor receptor-associated factor 6 (TraF6)/nF-κB signaling pathway in glomerular mesangial cells. For the clinical analysis, blood, urine and kidney tissue samples were collected from 58 patients diagnosed with primary iga nephropathy by renal biopsy. For the in vitro study, glomerular mesangial cells were divided into five groups: Control (con)-short hairpin rna (shrna) (control group); con-shrna + BaFF (20 ng/ml); con-shrna + BaFF + BaFF-rFc chimera protein (500 µg/ml); TraF6-shrna; and TraF6-shrna + BaFF (20 ng/ml). For the in vivo experiments, 60 Sprague-dawley rats were randomly divided into four groups: con-small interfering rna (sirna) (control group); con-sirna + iga (iga nephropathy group), BaFF-rFc chimera protein (2 µg/ml) + iga, and TraF6-sirna (0.2 µM) + iga. reverse transcription-quantitative Pcr was performed to evaluate the mrna expression levels of TraF6, connective tissue growth factor (cTGF), fibronectin (Fn) and nF-κBP65. Western blot analysis was used to detect the protein expression levels of TraF6, Fn, cTGF and phosphorylated-nF-κBP65 in glomerular mesangial cells and kidney tissues. The results revealed that plasma BaFF levels were positively correlated with the severity of pathological damage in patients with iga nephropathy. In vitro, BaFF induced the mrna and protein expression of TraF6, cTGF, Fn and nF-κBP65 in glomerular mesangial cells. after the BaFF-rFc chimera protein was added to inhibit the binding of BaFF and BaFF-receptor (-r), this effect was reduced. In vivo, inhibition of the effects of BaFF via injection with the BaFF-r Fc chimera protein reduced kidney damage in rats suffering from iga nephropathy. The effect on the expression of signaling pathway-associated proteins was also alleviated. in conclusion, BaFF enhanced the expression of fibroblast factors in the kidneys by activating the TraF6/nF-κB signaling pathway.

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MiR‐146a protects small intestine against ischemia/reperfusion injury by down‐regulating TLR4/TRAF6/NF‐κB pathway

Cited by 69 publications

References 32 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

Effect of Beta-Blockade on the Expression of Regulatory MicroRNA after Severe Trauma and Chronic Stress

BAFF is involved in the pathogenesis of IgA nephropathy by activating the TRAF6/NF‑κB signaling pathway in glomerular mesangial cells

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