CircC3P1 attenuated pro‐inflammatory cytokine production and cell apoptosis in acute lung injury induced by sepsis through modulating miR‐21

Jiang, Wenyang; Ren, Jie; Zhang, Xinghua; Lu, Zilong; Feng, Haojie; Yao, Xiaoli; Li, Donghang; Xiong, Rui; Fan, Tao; Qian, Geng

doi:10.1111/jcmm.15685

Cited by 45 publications

(24 citation statements)

References 24 publications

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“…Moreover, AAV-MEF2C treatment markedly suppressed sepsis-induced ALI by modulating miR-21. 22 During sepsis, increased numbers of TUNEL-positive cells in the lung sections were observed. 23 Currently, we demonstrated that CLP challenge elevated the number of TUNEL-positive cells in the lung section, which was further reduced by the overexpression of MEF2C, suggesting the anti-apoptosis effect of MEF2C in vivo.…”

Section: Discussionmentioning

confidence: 99%

MEF2C alleviates acute lung injury in cecal ligation and puncture (CLP)-induced sepsis rats by up-regulating AQP1

Liang

Guo

Liu

et al. 2021

aei

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Background: Sepsis is a systemic inflammatory response syndrome and leads to patient’s death. Objective: To investigate the effect of myocyte enhancer factor 2 (MEF2C) on acute lung injury (ALI) with sepsis and its possible mechanism.Material and Methods: The cecal ligation and puncture (CLP)-induced sepsis rat model was established. The lung injury was determined by lung wet–dry weight ratio, the concentration of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), Interlukin (IL)-6, IL-1β, and IL-10, were measured by the enzyme-linked-immunosorbent serologic assay kit. The cell apoptosis was detected by TUNEL staining assay.Results: Interestingly, MEF2C was down-regulated in this model. Moreover, adeno-associated virus (AAV)-MEF2C treatment markedly suppressed TNF-α, IL-1β, and IL-6 concentrations but promoted IL-10 concentration in serum in CLP-challenged rats. Besides, overexpression of MEF2C alleviates CLP-induced lung injury. Interestingly, AAV-MEF2C treatment was confirmed to suppress apoptosis in CLP-induced sepsis rats as well as promote aquaporin APQ1 expres-sion. Mechanistically, the rescue experiments indicated that MEF2C alleviated CLP-induced lung inflammatory response and apoptosis via up-regulating AQP1.Conclusion: In summary, overexpression of MEF2C suppressed CLP-induced lung inflamma-tory response and apoptosis via up-regulating AQP1, providing a novel therapeutic target for sepsis-induced ALI.

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Section: Discussionmentioning

confidence: 99%

MEF2C alleviates acute lung injury in cecal ligation and puncture (CLP)-induced sepsis rats by up-regulating AQP1

Liang

Guo

Liu

et al. 2021

aei

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“…Recent findings propose that circRNAs may play a role in regulating the patients' immune system, and misregulation of circRNAs might be an early event in sepsis [19][20][21]. It is well known that ARDS is one of the major consequences of septic shock [3].…”

Section: Discussionmentioning

confidence: 99%

CircN4bp1 Facilitates Sepsis-Induced Acute Respiratory Distress Syndrome through Mediating Macrophage Polarization via the miR-138-5p/EZH2 Axis

Zhao

Wang

Liu

et al. 2021

Mediators of Inflammation

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We recently reported the differential circRNA expression patterns of the pulmonary macrophages in sepsis-induced acute respiratory distress syndrome (ARDS) mice model by microarray analysis. However, their function and hidden molecular mechanism in regulation of macrophage activation and inflammation remain poorly understood. In this study, we found that circN4bp1was overexpressed in PBMC and monocytes, and its expression levels were correlated with a poor prognosis in sepsis induced ARDS patients induced by sepsis. Knockdown of circN4bp1 inhibited the lung injury and improved the long-time survival through blunting the M1 macrophage activation in cecal ligation and puncture- (CLP-) induced ARDS mice. Moreover, bioinformatics analysis predicated a circN4bp1/miR-138-5p ceRNA network, which was confirmed by luciferase reporter assay and RNA binding protein immunoprecipitation (RIP). CircN4bp1 affected macrophage differentiation by binding to miR-138-5p, thus regulating the expression of EZH2 in vivo and ex vivo. Lastly, the m6A level of circN4bp1was found to be elevated in ARDS mice; inhibition of m6A methyltransferase METTL3 blocked this response in vitro. Therefore, circN4bp1 can function as a miR-138-5p sponge for the modulation of macrophage polarization through regulation the expression of EZH2 and may serve as a potential target and/or prognostic marker for ARDS patients following sepsis.

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“…Recent ndings propose that circRNAs may play a role in regulating the patients' immune system and misregulation of circRNAs might be an early event in sepsis [21,22,23] . It is well known that ARDS is one of the major consequences of septic shock [3] .…”

Section: Discussionmentioning

confidence: 99%

CircN4bp1 Facilitates Sepsis-Induced Acute Respiratory Distress Syndrome Through Mediating Macrophage Polarization via the miR-138-5p/EZH2 Axis

et al. 2021

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BackgroundWe recently reported the differential circRNAs expression patterns of the pulmonary macrophages in sepsis induced ARDS mice model by microarray analysis; However, their function and hidden molecular mechanism in regulation of macrophage activation and in ammation remains poorly understood. MethodsIn this study, serum were obtained from ARDS patients post sepsis and control subjects. Mice were subjected to Cecal ligation and puncture (CLP) surgery and intravenously injected with si-circN4bp1 plasmid transfected macrophages. Raw264.7 cells and MH-S cells were transfected with circN4bp1 overexpression or silence vectors and then polarized as M1 or M2 macrophages in vitro. ResultsWe rstly examined the quantitative expression and localization of circN4bp1 in macrophages by Realtime PCR and uorescence in situ hybridization (FISH), and found that circN4bp1 was overexpressed in PBMC and monocytes and its expression levels were correlated with a poor prognosis in ARDS patients induced by sepsis. In CLP-induced ARDS mice, we demonstrated that knockdown of circN4bp1 inhibited the lung injury and in ammatory cytokine release, and improved the long-time survival through blunting the M1 macrophage activation. Moreover, bioinformatics analysis predicated a circN4bp1/miR-138-5p ceRNA network, which was con rmed by Luciferase reporter assay and RNA binding protein immunoprecipitation (RIP). In vitro experiments, we indicated that circN4bp1 affected macrophage differentiation by binding to miR-138-5p, thus regulating the expression of EZH2. Lastly, we found that the m6A level of circN4bp1 was elevated in ARDS mice; inhibition of m6A methyltransferases METTL3 blocked this response in vitro. ConclusionsThese data suggest that circN4bp1 can function as a miR-138-5p sponge for the regulation of macrophage polarization and may serve as a potential target and/or prognostic marker for ARDS patients following sepsis.

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CircC3P1 attenuated pro‐inflammatory cytokine production and cell apoptosis in acute lung injury induced by sepsis through modulating miR‐21

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 45 publications

References 24 publications

MEF2C alleviates acute lung injury in cecal ligation and puncture (CLP)-induced sepsis rats by up-regulating AQP1

MEF2C alleviates acute lung injury in cecal ligation and puncture (CLP)-induced sepsis rats by up-regulating AQP1

CircN4bp1 Facilitates Sepsis-Induced Acute Respiratory Distress Syndrome through Mediating Macrophage Polarization via the miR-138-5p/EZH2 Axis

CircN4bp1 Facilitates Sepsis-Induced Acute Respiratory Distress Syndrome Through Mediating Macrophage Polarization via the miR-138-5p/EZH2 Axis

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