MicroRNA‑146a/Toll‑like receptor 4 signaling protects against severe burn‑induced remote acute lung injury in rats via anti‑inflammation

Luo, Jianmin; Zhan, Jie; You, Haoyuan; Cheng, Xing

doi:10.3892/mmr.2018.8877

Cited by 4 publications

(4 citation statements)

References 22 publications

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“…MicroRNAs (miRNAs) are a class of highly conserved, single-stranded, short noncoding RNAs that suppress the expression of protein-coding genes at the posttranscriptional level [14]. Emerging evidence reveals that miRNAs play a major role in the amelioration of various inflammatory diseases, including ALI [15][16][17]. Recent studies in mouse ALI model showed that miRNA expression profiles are altered after ALI, and modulation of miRNA expression can affect the development of ALI [16,18,19].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of miR-221 alleviates LPS-induced acute lung injury via inactivation of SOCS1/NF-κB signaling pathway

et al. 2019

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The role of inflammation response has been well documented in the development of acute lung injury (ALI). However, little is known about the functions of miRNAs in the regulation of inflammation in ALI. The aim of this study was to explore the effects of miRNAs in the regulation of inflammation in ALI and to elucidate the biomolecular mechanisms responsible for these effects. The expression profiles of miRNAs in lung tissues from lipopolysaccharide (LPS)-induced ALI mice model were analyzed using a microarray. It was observed that microRNA-221-3p (miR-221) was significantly increased in lung tissues in ALI mice. The inhibition of miR-221 attenuated lung injury including decreased lung W/D weight ratio and lung permeability and survival rates of ALI mice, as well as apoptosis, whereas its agomir-mediated upregulation exacerbated the lung injury. Concomitantly, miR-221 inhibition significantly reduced LPS-induced pulmonary inflammation, while LPS-induced pulmonary inflammation was aggravated by miR-221 upregulation. Of note, suppressor of cytokine signaling-1 (SOCS1), an effective suppressor of the NF-κB signaling pathway, was found to be a direct target of miR-221 in RAW264.7 cells. Overexpression of SOCS1 by pcDNA-SOCS1 plasmids markedly reversed the miR-221 inhibition-mediated inhibitory effects on inflammation and apoptosis in LPS-treated RAW264.7 cells. Finally, it was found that miR-221 inhibition suppressed LPS induced the activation of the NF-κB signaling pathway, as demonstrated by downregulation of phosphorylated-IκBα, p-p65 and upregulation of IκBα, whilst miR-221 overexpression had an opposite result in ALI mice. Our findings demonstrate that inhibition of miR-221 can alleviate LPS-induced inflammation via inactivation of SOCS1/NF-κB signaling pathway in ALI mice.

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Section: Introductionmentioning

confidence: 99%

Inhibition of miR-221 alleviates LPS-induced acute lung injury via inactivation of SOCS1/NF-κB signaling pathway

et al. 2019

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“…Furthermore, lung IR injury can be alleviated by inhibiting the activation of TLR 2/4 activity (30). Certain studies have shown that miRNA-146a reduces lung injury via the TLR4 / NFκB signaling pathway (31). Similarly, other studies have reported the function of miR-21 in the development of severe primary graft dysfunction by activating the key components of the TLR pathway (27).…”

Section: Discussionmentioning

confidence: 99%

MiRNA-122 promotes ischemia-reperfusion injury after lung transplantation via the TLR signaling pathway

Lu,

Wang,

Liu

et al. 2024

Preprint

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Background: MiRNAs have been recently implicated in the pathogenesis underlying ischemia-reperfusion (IR) injury. We investigated the miRNAs expression profiles in the early stages after lung transplantation (LT) and studied the involvement of Toll-like receptor(TLR) signaling pathway in lung IR injury following LT. Methods: We established the left LT model in mice, The mice were injected with a miRNA-122 specific inhibitor, following which pathological changes in the lung tissue were studied using different lung injury indicators. In addition, we performed deep sequencing in transplanted lung tissues to indentify differentially expressed (DE) miRNAs and their target genes. Results: A total of 12DE miRNAs were selected and 2,476 target genes were identified; The gene ontology (GO) enrichment analysis predicted 6,063 terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis predicted 1,554 biological pathways. Compared with the control group, inhibiting the expression of miRNA-122 significantly reduced the lung injury and lung W / D ratio (p<0.05). In addition, the activity of myeloperoxidase (MPO) and expression of tumor necrosis factor (TNF)-α and TLR2/4 decreased (p<0.05); whereas the expression of interleukin-10(IL-10) expression levels increased (p<0,05). Furthermore, the inhibition of miRNA-122 suppressed the IR injury-induced activation of the TLR signaling pathway. Conclusions: Our findings showed the differential expression of several miRNAs in the early inflammatory response following LT. Of these, miRNA-122 promoted the IR injury following LT, whereas its inhibition prevented IR injury in a TLR-dependent manner.

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“…MiR-146a-5p is involved in epithelial-fibroblast communication in the lungs, and the pro-inflammatory phenotype of COPD fibroblasts that have been shown to result from dysregulation of epithelial-fibroblast interaction, partly due to the reduced ability of COPD-derived fibroblasts to upregulate miR-146a-5p to counter-regulate pro-inflammatory activity 40 . Furthermore, downregulation of mir-146-a/TLR4 signaling protects against sever burn-induces remote acute lung injury via anit-inflammation 41 . Down-regulation of miR-146a-5p may thus reflect a pro-inflammatory process in grain dust exposed workers.…”

Section: Discussionmentioning

confidence: 99%

Circulating miRNAs as molecular markers of occupational grain dust exposure

Straumfors

Duale

Foss

et al. 2020

Sci Rep

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Dust from grain and feed production may cause adverse health effects in exposed workers. In this study we explored circulating miRNAs as potential biomarkers of occupational grain dust exposure. Twenty-two serum miRNAs were analyzed in 44 grain dust exposed workers and 22 controls. Exposed workers had significantly upregulated miR-18a-5p, miR-124-3p and miR-574-3p, and downregulated miR-19b-3p and miR-146a-5p, compared to controls. Putative target genes for the differentially expressed miRNAs were involved in a range of Kyoto Encyclopedia of Genes and Genomes signaling pathways, and 'Pathways in cancer' and 'Wnt signaling pathway' were common for all the five miRNAs. MiRNA-diseases association analysis showed a link between the five identified miRNAs and several lung diseases terms. A positive correlation between miR-124-3p, miR-18a-5p, and miR-574-3p and IL-6 protein level was shown, while miR-19b-3p was inversely correlated with CC-16 and sCD40L protein levels. Receiver-operating characteristic analysis of the five miRNA showed that three miRNAs (miR-574-3p, miR-124-3p and miR-18a-5p) could distinguish the grain dust exposed group from the control group, with miR-574-3p as the strongest predictor of grain dust exposure. In conclusion, this study identified five signature miRNAs as potential novel biomarkers of grain dust exposure that may have potential as early disease markers. Workers at grain elevators and animal feed mills are exposed to grain dust containing a complex mixture of inorganic and organic particles from soil, plants, insects and microorganisms, and includes components such as endotoxins, β-1,3-glucans and mycotoxins 1,2. The individual dust components have the ability to induce inflammatory and allergic responses, and symptoms from the airways are frequently observed among grain handlers 3-8. Endotoxin has been proposed as a target for measurements of occupational health hazard of grain dust 9 , but depending on the grain dust composition, other components in the dust may be stronger associated with health effects. Diverging exposure-response relationships have indeed been observed between studies 2,3,10-12. Although exact mechanisms are not completely elucidated, the pathological response to grain dust exposure may include activation of inflammatory and allergic pathways. miRNAs are small non-coding RNA molecules that regulate gene expression by binding to specific mRNAs, which leads to either degradation of the mRNA or inhibition of translation, thus suppressing gene activity 13. Several studies have suggested that the toxicity of environmental chemicals are mediated by miRNAs 14 , and particular miRNA profiles have been associated with different diseases, such as asthma, COPD and cancer 15. Little is known about the miRNA induction following grain dust exposure. However, it is shown that miR-146a are induced by LPS and other proinflammatory mediators such as TNFα, IL-1β and CD40L 16. Epigenetic studies in mice models suggests a role for increased miR-146a in allergic rhinitis 17. Reduced exp...

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MicroRNA‑146a/Toll‑like receptor 4 signaling protects against severe burn‑induced remote acute lung injury in rats via anti‑inflammation

Cited by 4 publications

References 22 publications

Inhibition of miR-221 alleviates LPS-induced acute lung injury via inactivation of SOCS1/NF-κB signaling pathway

Inhibition of miR-221 alleviates LPS-induced acute lung injury via inactivation of SOCS1/NF-κB signaling pathway

MiRNA-122 promotes ischemia-reperfusion injury after lung transplantation via the TLR signaling pathway

Circulating miRNAs as molecular markers of occupational grain dust exposure

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