miR‑23a downregulation modulates the inflammatory response by targeting ATG12‑mediated autophagy

Xiang, Shijun; Cao, Dai-Yin; Chen, Juan; Nie, Yao; Jiang, Zhiyi; Chen, Minying; Wu, Jianfeng; Guan, Xiangdong

doi:10.3892/mmr.2018.9081

Cited by 19 publications

(17 citation statements)

References 37 publications

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“…There are not many reports on the role of miRNA-23a on the regulation of inflammation. Interestingly, during septic insult, miRNA-23a expression was found to be decreased which was associated with increased autophagy and suppression of inflammatory mediators ( Si et al, 2018 ). In this study, miRNA-23a was shown to target Autophagy related 12 (ATG12), which regulates autophagy ( Si et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

The Endocannabinoid Anandamide Attenuates Acute Respiratory Distress Syndrome by Downregulating miRNA that Target Inflammatory Pathways

et al. 2021

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Acute respiratory distress syndrome (ARDS) is defined as a type of respiratory failure that is caused by a variety of insults such as pneumonia, sepsis, trauma and certain viral infections. In this study, we investigated the effect of an endocannabinoid, anandamide (AEA), on ARDS induced in the mouse by Staphylococcus Enterotoxin B (SEB). Administration of a single intranasal dose of SEB in mice and treated with exogenous AEA at a dose of 40 mg/kg body weight led to the amelioration of ARDS in mice. Clinically, plethysmography results indicated that there was an improvement in lung function after AEA treatment accompanied by a decrease of inflammatory cell infiltrate. There was also a significant decrease in pro-inflammatory cytokines IL-2, TNF-α, and IFN-γ, and immune cells including CD4+ T cells, CD8+ T cells, Vβ8+ T cells, and NK+ T cells in the lungs. Concurrently, an increase in anti-inflammatory phenotypes such as CD11b + Gr1+ Myeloid-derived Suppressor Cells (MDSCs), CD4 + FOXP3 + Tregs, and CD4+IL10 + cells was observed in the lungs. Microarray data showed that AEA treatment in ARDS mice significantly altered numerous miRNA including downregulation of miRNA-23a-3p, which caused an upregulation of arginase (ARG1), which encodes for arginase, a marker for MDSCs, as well as TGF-β2, which induces Tregs. AEA also caused down-regulation of miRNA-34a-5p which led to induction of FoxP3, a master regulator of Tregs. Transfection of T cells using miRNA-23a-3p or miRNA-34a-5p mimics and inhibitors confirmed that these miRNAs targeted ARG1, TGFβ2 and FoxP3. In conclusion, the data obtained from this study suggests that endocannabinoids such as AEA can attenuate ARDS induced by SEB by suppressing inflammation through down-regulation of key miRNA that regulate immunosuppressive pathways involving the induction of MDSCs and Tregs.

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Section: Discussionmentioning

confidence: 99%

The Endocannabinoid Anandamide Attenuates Acute Respiratory Distress Syndrome by Downregulating miRNA that Target Inflammatory Pathways

et al. 2021

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“…For example, miR-145 is highly expressed in vascular smooth muscle cells and has been reported to promote their switching to neointimal proliferating cells 105,106 and to regulate the transforming growth factor-β signalling pathway 103 . Increased levels of miR-23a contribute to cardiomyocyte apoptosis and may promote inflammatory responses by blocking macrophage autophagy activity 107,108 . However, improved understanding and characterization of the molecular and cellular mechanisms underlying the different roles of miRs during Kawasaki disease require further studies with animal models.…”

Section: Pathophysiology Of Kawasaki Diseasementioning

confidence: 99%

Kawasaki disease: pathophysiology and insights from mouse models

2020

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Kawasaki disease is a systemic vasculitis that affects infants and young children 1-3. Kawasaki disease is now the leading cause of acquired heart disease among children in North America, Europe and Japan 4,5. The cardiovascular sequelae resulting from childhood Kawasaki disease are increasingly recognized to extend into adulthood, and the disease is no longer considered self-limiting 6-9. The triggering agents for Kawasaki disease remain unidentified; however, results from our laboratory 10,11 and others 12,13 are consistent with the interpretation that a conventional antigen is probably responsible. Coronary arteritis and predominantly coronary artery aneurysms (CAAs) occur in up to 30% of untreated children, although this rate is reduced to 5-7% in children treated with high-dose intravenous immunoglobulin (IVIG) 3,14,15. IVIG treatment leads to CAA regression in 60-75% of patients with Kawasaki disease 16,17. However, the exact mechanisms by which IVIG reduces the rate of cardiovascular complications are unknown 18. Up to 15-20% of patients with Kawasaki disease do not respond to IVIG treatment, and these individuals have an increased rate of CAA development 3,15,19-21. Kawasaki disease is associated with infiltration of the coronary artery wall by a broad variety of innate and adaptive immune cells. Immunohistochemical analysis of human post-mortem tissues shows accumulation in the arterial wall of monocytes, macrophages and neutrophils 22,23 , and the presence of activated CD8 + T cells 24 as well Aetiological agents The causative agents initiating the disease have still not been identified >50 years after the first description of Kawasaki disease. However, the trigger is suspected to be of viral origin and to enter the body through the

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“…ATG12 directly promotes phagocytic elongation and autophagosome maturation, and can be targeted by miR-23a. In sepsis, down-regulation of miR-23a mitigates the inhibition of autophagy, leading to the suppression of inflammatory mediator (Si et al, 2018). The study found that over-expression of miR-335-5p induced autophagy by activating the AMPK/ULK1 (AMP-activated protein kinase/unc-51 like autophagy activating kinase 1) signaling pathway and attenuating the inflammatory response in a mouse model of sepsis (Gao et al, 2018).…”

Section: Regulation Of Autophagy In Sepsis and Its Mechanism Of Actionmentioning

confidence: 99%

The Role of Autophagy in Sepsis: Protection and Injury to Organs

et al. 2019

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Sepsis is a systemic inflammatory disease with infection, and autophagy has been shown to play an important role in sepsis. This review summarizes the main regulatory mechanisms of autophagy in sepsis and its latest research. Recent studies have shown that autophagy can regulate innate immune processes and acquired immune processes, and the regulation of autophagy in different immune cells is different. Mitophagy can select damaged mitochondria and remove it to deal with oxidative stress damage. The process of mitophagy is regulated by other factors. Non-coding RNA is also an important factor in the regulation of autophagy. In addition, more and more studies in recent years have shown that autophagy plays different roles in different organs. It tends to be protective in the lungs, heart, kidneys, and brain, and tends to be damaging in skeletal muscle. We also mentioned that some drugs can regulate autophagy. The process of modulating autophagy through drug intervention appears to be a new potential hope for the treatment of sepsis.

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miR‑23a downregulation modulates the inflammatory response by targeting ATG12‑mediated autophagy

Cited by 19 publications

References 37 publications

The Endocannabinoid Anandamide Attenuates Acute Respiratory Distress Syndrome by Downregulating miRNA that Target Inflammatory Pathways

The Endocannabinoid Anandamide Attenuates Acute Respiratory Distress Syndrome by Downregulating miRNA that Target Inflammatory Pathways

Kawasaki disease: pathophysiology and insights from mouse models

The Role of Autophagy in Sepsis: Protection and Injury to Organs

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