MicroRNA-144-3p enhances LPS induced septic acute lung injury in mice through downregulating Caveolin-2

Xu, Rui-Ming; Shao, Zhengyi; Cao, Qiumei

doi:10.1016/j.imlet.2020.12.015

Cited by 15 publications

(8 citation statements)

References 25 publications

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“…These results suggest that upregulation of miR-144 in the lungs promotes inflammatory diseases. A recent study reported that lung inflammation and cell apoptosis induced by LPS were alleviated by injection of a miR-144 antagomir (41). However, in our study, deletion of the miR-144/451 cluster aggravated sepsis-induced lung epithelial injury, indicating that miR-451 might have played a crucial role in determining sepsis severity.…”

Section: Discussioncontrasting

confidence: 82%

Deletion of the miR-144/451 cluster aggravates lethal sepsis-induced lung epithelial oxidative stress and apoptosis

Wu¹,

Yuan²,

Liu³

et al. 2022

Ann Transl Med

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Background: Sepsis is associated with a high mortality rate. A major cause of death in sepsis patients is respiratory failure, which is characterized by oxidative injury, epithelial apoptosis, and increased lung permeability. MicroRNAs (miRs) are important regulators of sepsis progression.Methods: This study aimed to explore the role of miR-144/451 in sepsis in mice. Experimental sepsis was induced in C57BL/6 mice by cecal ligation and puncture (CLP).Results: CLP significantly induced systemic inflammation, lung permeability, and lung epithelial apoptosis with downregulated messenger RNA (mRNA) levels of antioxidant enzymes. The miR-144/451 knockout mice had a lower 48-hour survival rate, higher plasma tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) levels, and greater pulmonary permeability compared with wild-type mice after CLP. CLP also markedly increased interstitial hemorrhage, collapsed more alveolar sacs, and increased the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive and Bcl-2-associated X (Bax)-positive cells in miR-144/451 knockout lung tissues, with elevated mRNA levels of Bax and reduced activities of catalase (Cat), glutathione peroxidase 1(Gpx1). MiR-451 negatively regulated 14-3-3ζ expression evidenced in miR-144/451 knockout lungs and the A549 cell line. In lipopolysaccharide (LPS)-induced A549 cells, miR-451 overexpression remarkably suppressed the production of reactive oxygen species, inhibited cell apoptosis, and enhanced levels of FoxO3 protein and related enzymes.Conclusions: Deletion of the miR-144/451 cluster aggravated sepsis-induced oxidative injury of lung epithelial cells.

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Section: Discussioncontrasting

confidence: 82%

Deletion of the miR-144/451 cluster aggravates lethal sepsis-induced lung epithelial oxidative stress and apoptosis

Wu¹,

Yuan²,

Liu³

et al. 2022

Ann Transl Med

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“…The study conducted by Xu demonstrated that the expression of miR-144-3p is elevated in sepsis-induced ALI, both in patients and in mouse models. A further evaluation of miR-144-3p in mice led to the discovery that it acts through the inhibition of Caveolin2, thus activating the JAK/STAT pathway and increasing the production of pro-inflammatory factors and cell apoptosis [ 199 ]. The downregulation of mir-19a-3p was found to improve inflammation and ALI induced by sepsis in both in vivo and in vitro experiments, as the reduction in pro-inflammatory cytokines demonstrated.…”

Section: Resultsmentioning

confidence: 99%

Expression of MicroRNAs in Sepsis-Related Organ Dysfunction: A Systematic Review

Maiese

Scatena

Costantino

et al. 2022

IJMS

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Sepsis is a critical condition characterized by increased levels of pro-inflammatory cytokines and proliferating cells such as neutrophils and macrophages in response to microbial pathogens. Such processes lead to an abnormal inflammatory response and multi-organ failure. MicroRNAs (miRNA) are single-stranded non-coding RNAs with the function of gene regulation. This means that miRNAs are involved in multiple intracellular pathways and thus contribute to or inhibit inflammation. As a result, their variable expression in different tissues and organs may play a key role in regulating the pathophysiological events of sepsis. Thanks to this property, miRNAs may serve as potential diagnostic and prognostic biomarkers in such life-threatening events. In this narrative review, we collect the results of recent studies on the expression of miRNAs in heart, blood, lung, liver, brain, and kidney during sepsis and the molecular processes in which they are involved. In reviewing the literature, we find at least 122 miRNAs and signaling pathways involved in sepsis-related organ dysfunction. This may help clinicians to detect, prevent, and treat sepsis-related organ failures early, although further studies are needed to deepen the knowledge of their potential contribution.

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“…In our study, we analyzed miRNAs targeting key genes and identified a total of 113 miRNAs and 113 mRNA-miRNA relationship pairs, including miR-144-3P, miR-301a-3p, miR-301b-3p, and miR-103a-3p. Previous studies have shown that miR-144-3p can promote LP-induced sepsis by downregulating caveolin-2, activating the JAK/STAT signaling pathway (35). The long-chain noncoding RNA CASC2 can reduce lung epithelial cell apoptosis and improve ALI by regulating the miR-144-3p/AQP1 axis (36).…”

Section: Discussionmentioning

confidence: 99%

Analysis and Identification of Ferroptosis-Related Gene Signature for Acute Lung Injury

Wang,

Yue,

et al. 2023

Shock

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Background Recent studies have shown that ferroptosis is involved in the evolution of acute lung injury (ALI), a serious respiratory pathological process leading to death. However, the regulatory mechanisms underlying ferroptosis in ALI remain largely unknown. The current study analyzed and identified a ferroptosis-related gene signature for ALI. Methods Key genes associated with ferroptosis in ALI were identified by bioinformatics analysis. GSE104214, GSE18341, and GSE17355 datasets were downloaded from the Gene Expression Omnibus database. The signature genes were screened by least absolute shrinkage and selection operator (LASSO) regression, and the key genes of ALI were screened by weighted correlation network analysis (WGCNA), followed by immune infiltration analysis and functional enrichment analysis. In addition, mRNA expression of key genes in the lungs of mice with hemorrhagic shock and sepsis was verified. Results A total of 2132 differential genes were identified by various analyses, and nine characteristic genes were detected using Lasso regression. We intersected nine signature genes with WGCNA module genes and finally determined four key genes (PROK2, IL6, TNF, SLC7A11). All four key genes were closely correlated with immune cells and regulatory genes of ALI, and the expression of the four genes was significantly different in the lung tissues of hemorrhagic shock and sepsis models. Besides, the ferroptosis related molecules GPX4 and ACSL4 showed remarkable difference in these models. Conclusion These results indicate that PROK2, IL6, TNF, SLC7A11 may be key regulatory targets of ferroptosis during ALI. This study proved that ferroptosis is a common pathophysiological process in three ALI models.

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MicroRNA-144-3p enhances LPS induced septic acute lung injury in mice through downregulating Caveolin-2

Cited by 15 publications

References 25 publications

Deletion of the miR-144/451 cluster aggravates lethal sepsis-induced lung epithelial oxidative stress and apoptosis

Deletion of the miR-144/451 cluster aggravates lethal sepsis-induced lung epithelial oxidative stress and apoptosis

Expression of MicroRNAs in Sepsis-Related Organ Dysfunction: A Systematic Review

Analysis and Identification of Ferroptosis-Related Gene Signature for Acute Lung Injury

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