UMLS:C0036690 - FACTA Search

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Query: UMLS:C0036690 (sepsis)
59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenosine deaminase acting on RNA 1 (ADAR1), a double-stranded RNA-editing enzyme that converts adenosine (A) to inosine (I), has been identified as a modulator of immune responses. However, the role of ADAR1 in small intestinal homeostasis during sepsis remains unclear. In this study, we examined the role of ADAR1 on intestinal inflammation in a murine model of sepsis. We found that ADAR1 was highly expressed in "septic" macrophages and small intestinal tissue of septic mice. Deletion of ADAR1 in "septic" macrophages led to rapid apoptosis. In addition, suppression of ADAR1 in "septic" macrophages significantly enhanced inflammation, while over-expression of ADAR1 significantly suppressed the level of inflammatory cytokines. Furthermore, suppression of ADAR1 in septic mice significantly enhanced inflammation and intestinal damage, while enhanced ADAR1 expression resulted in reduced damage and inflammation. Finally, over-expression of ADAR1 improved survival of septic mice. In conclusion, we have identified a novel ADAR1 protective effect for maintaining intestinal homeostasis. Our findings may provide a new targeted therapy for sepsis treatment.
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PMID:ADAR1 prevents small intestinal injury from inflammation in a murine model of sepsis. 2941 24

Adenosine deaminase acting on RNA 1 (ADAR1) has been shown to participate in the regulation of endothelial cells (ECs), as well as local and systemic inflammatory responses. Here, we find that bacterial lipopolysaccharide (LPS)-induced upregulation of ADAR1 in lung ECs is impaired in aged mice, an animal model with high rates of sepsis and mortality. Endothelial cell-specific ADAR1 knockout (ADAR1^ECKO ) mice suffer from higher mortality rates, aggravated lung injury, and increased vascular permeability under LPS challenge. In primary ADAR1 knockout ECs, expression of the melanoma differentiation-associated gene 5 (MDA5), a downstream effector of ADAR1, is significantly elevated. MDA5 knockout completely rescues the postnatal offspring death of ADAR1^ECKO mice. However, there is no reduction in mortality or apoptosis in lung cells of ADAR1^ECKO /MDA5^-/- mice challenged with LPS, indicating the involvement of an MDA5-independent mechanism in this process.
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PMID:Endothelial cell-specific deficiency of the adenosine deaminase ADAR1 aggravates LPS-induced lung injury in mice via an MDA5-independent pathway. 3204 61

Adenosine deaminase acting on double-stranded RNA 1 (ADAR1) mediates adenosine-to-inosine (A-to-I) RNA editing events. ADAR1 is highly expressed in "septic" macrophages and in small intestinal tissues of mice with sepsis. Overexpression of ADAR1 suppresses inflammation and intestinal damage. However, the specific underlying mechanism is unclear. This study was conducted to explore how microRNA (miRNA) regulates the anti-inflammatory mechanism of macrophages following ADAR1 upregulation. A murine sepsis model was established by cecal ligation and puncture (CLP). Mice were randomly assigned to sham, CLP, and CLP+ADAR1 groups. Hematoxylin and eosin (HE) staining and fluorescence isothiocyanate-dextran were used to evaluate intestinal injury and permeability. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting, and Luminex assays were performed to detect changes in the expression of inflammatory cytokines. Adenoviruses were used to express ADAR1 in RAW 264.7 cells. Ribonucleoprotein immunoprecipitation analysis was conducted to detect the binding of ADAR1 and miRNAs. A dual-luciferase reporter assay was used to detect the binding of miRNAs and regulatory factors. We observed that ADAR1 significantly increased the expression of suppressor of cytokine signaling 3 (SOCS3) in macrophages and reduced the expression of interleukin-6 in macrophages and the serum, thereby reducing intestinal permeability and mucosal injury in mice with sepsis. The RNA-ribonucleoprotein immunoprecipitation binding assay and qRT-PCR demonstrated a direct interaction between ADAR1 and pri-miR-30a. The luciferase assay demonstrated that SOCS3 was significantly inhibited by miR-30a-5p, the mature product of miR-30a. Thus, ADAR1 exerts a protective effect against sepsis by reducing inflammation and organ damage via the ADAR1-miR-30a-SOCS3 axis.
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PMID:ADAR1 Alleviates Inflammation in a Murine Sepsis Model via the ADAR1-miR-30a-SOCS3 Axis. 3227 31