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

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IntroductionCircular RNAs (circRNAs) have been linked to regulate macrophage polarization and subsequent inflammation in sepsis. However, the underlying mechanism and the function of circRNAs in macrophage pyroptosis in pneumonia-induced sepsis are still unknown.MethodsIn this study, we screened the differentially expressed circRNAs among the healthy individuals, pneumonia patients without sepsis and pneumonia-induced sepsis patients in the plasma by RNA sequencing (RNA-seq). Then we evaluated macrophage pyroptosis in sepsis patients and in vitro LPS/nigericin activated THP-1 cells. The lentiviral recombinant vector for circ_0075723 overexpression (OE-circ_0075723) and circ_0075723 silence (sh-circ_0075723) were constructed and transfected into THP-1 cells to explore the potential mechanism of circ_0075723 involved in LPS/nigericin induced macrophage pyroptosis.ResultsWe found circ_0075723, a novel circRNA that was significantly downregulated in pneumonia-induced sepsis patients compared to pneumonia patients without sepsis and healthy individuals. Meanwhile, pneumonia-induced sepsis patients exhibited activation of NLRP3 inflammasome and production of the pyroptosis-associated pro-inflammatory cytokines IL-1β and IL-18. circ_0075723 inhibited macrophage pyroptosis via sponging miR-155-5p which promoted SHIP1 expression directly. Besides, we found that circ_0075723 in macrophages promoted VE-cadherin expression in endothelial cells through inhibiting the release of NLRP3 inflammasome-related cytokines, IL-1β and IL-18, and protects endothelial cell integrity.DiscussionOur findings propose a unique approach wherein circ_0075723 suppresses macrophage pyroptosis and inflammation in pneumonia-induced sepsis via sponging with miR-155-5p and promoting SHIP1 expression. These findings indicate that circRNAs could be used as possible potential diagnostic and therapeutic targets for pneumonia-induced sepsis.

Section: Introductionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 97%

CircRNA_0075723 protects against pneumonia-induced sepsis through inhibiting macrophage pyroptosis by sponging miR-155-5p and regulating SHIP1 expression

Yang

Zhao²,

Ji³

et al. 2023

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“…The increase in pathogen load or the release of “waterfall” inflammatory factors, in turn, stimulates the pulmonary adaptive immune system, in which T and B cells are activated and work together with the innate immune response in order to release SIgA, defensins, lysozyme, and complement (C3a, C5a), which then clear the pathogenic bacteria. Irreversible PALI is caused by the immune system paralysis for the imbalance between Th17 and Tregs, the increased antibody dependence-enhancement, the abnormal increase in complement, and the inactivation of innate immune cell function ( 116 , 118 , 119 ).…”

Section: Mechanisms Of Ali Caused By Intestinal Bacterial Dysbiosismentioning

confidence: 99%

Intestinal Microbiota - An Unmissable Bridge to Severe Acute Pancreatitis-Associated Acute Lung Injury

Wang

Liu

et al. 2022

Severe acute pancreatitis (SAP), one of the most serious abdominal emergencies in general surgery, is characterized by acute and rapid onset as well as high mortality, which often leads to multiple organ failure (MOF). Acute lung injury (ALI), the earliest accompanied organ dysfunction, is the most common cause of death in patients following the SAP onset. The exact pathogenesis of ALI during SAP, however, remains unclear. In recent years, advances in the microbiota-gut-lung axis have led to a better understanding of SAP-associated lung injury (PALI). In addition, the bidirectional communications between intestinal microbes and the lung are becoming more apparent. This paper aims to review the mechanisms of an imbalanced intestinal microbiota contributing to the development of PALI, which is mediated by the disruption of physical, chemical, and immune barriers in the intestine, promotes bacterial translocation, and results in the activation of abnormal immune responses in severe pancreatitis. The pathogen-associated molecular patterns (PAMPs) mediated immunol mechanisms in the occurrence of PALI via binding with pattern recognition receptors (PRRs) through the microbiota-gut-lung axis are focused in this study. Moreover, the potential therapeutic strategies for alleviating PALI by regulating the composition or the function of the intestinal microbiota are discussed in this review. The aim of this study is to provide new ideas and therapeutic tools for PALI patients.

“…Furthermore, circRNAs can lead to the polarization of tumor-associated macrophages to M1 or M2 macrophages. One study showed that circN4 bp1 could act as a miR-138-5p sponge for the modulation of macrophage polarization through the regulation of the expression of EZH2 (a histone methyltransferase) ( 124 ). Moreover, circRNA Cdyl, circPrkcsh and circPPM1F were found to play a role in inducing M1 macrophage polarization ( 118 , 125 , 126 ).…”

Section: Roles Of Circrnas In Immune-related Diseasesmentioning

confidence: 99%

Past, Present and Future: The Relationship Between Circular RNA and Immunity

Huang

et al. 2022

The immune system has evolved since the birth of humans. However, immune-related diseases have not yet been overcome due to the lack of expected indicators and targeting specificity of current medical technology, subjecting patients to very uncomfortable physical and mental experiences and high medical costs. Therefore, the requirements for treatments with higher specificity and indicative ability are raised. Fortunately, the discovery of and continuous research investigating circular RNAs (circRNAs) represent a promising method among numerous methods. Although circRNAs wear regarded as metabolic wastes when discovered, as a type of noncoding RNA (ncRNA) with a ring structure and wide distribution range in the human body, circRNAs shine brilliantly in medical research by virtue of their special nature and structure-determined functions, such as high stability, wide distribution, high detection sensitivity, acceptable reproducibility and individual differences. Based on research investigating the role of circRNAs in immunity, we systematically discuss the hotspots of the roles of circRNAs in immune-related diseases, including expression profile analyses, potential biomarker research, ncRNA axis/network construction, impacts on phenotypes, therapeutic target seeking, maintenance of nucleic acid stability and protein binding research. In addition, we summarize the current situation of and problems associated with circRNAs in immune research, highlight the applications and prospects of circRNAs in the treatment of immune-related diseases, and provide new insight into future directions and new strategies for laboratory research and clinical applications.