MicroRNA miR-223 constrains lethal inflammation during Mycobacterium tuberculosis infection
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE39163 | GEO | 2014/04/21
SECONDARY ACCESSION(S): PRJNA170123
REPOSITORIES: GEO
Similar Datasets
Project description:The molecular mechanisms that control innate cell recruitment during chronic infection and inflammation, such as tuberculosis (TB), are incompletely understood. During TB, myeloid cells infiltrate the lung and sustain local inflammation. We identified microRNA (miR)-223 as one of the most abundant noncoding RNAs in lung parenchyma of TB patients and susceptible mice. MiR-223 controlled lung recruitment of myeloid cells, and consequently, neutrophil-driven lethal inflammation, by directly targeting the chemoattractants CXCL2, CCL3 and IL-6. Our study reveals an essential role for a single miR in TB. Moreover, we identify new targets for and assign novel biological functions to miR-223. By regulating leukocyte chemotaxis via chemoattractants, miR223 is critical for control of TB and probably other nonresolving inflammatory diseases. MicroRNAs expression analysis in whole blood from 8 TB and 8 TST+ subjects. The samples were collected at Makerere University in Kampala, Uganda. Gene expression analysis of whole blood and lung tissue of C57/BL6 and miR-223-/- mouse strains (8-12 weeks of age) after Mtb aerosol infection. Samples were collected at 7, 14 and 21 days post infection.
2014-04-21 | E-GEOD-39163 | biostudies-arrayexpress
Project description:MicroRNA-223, a principal myeloid-specific anti-inflammatory microRNA, is dysregulated in numerous inflammatory conditions and cancers. We found that miR-223 deficient zebrafish displayed augmented neutrophilic inflammation, which was due primarily to elevated activation of the canonical NF-B pathway. To our surprise, the NF-B over-activation was restricted to the basal epithelial cells, a squamous layer permeable to oxygen and chemicals. MiR-223 was expressed in epithelial cells and directly down-regulated multiple components in the NF-B signaling pathway in zebrafish and human. Both phagocytic and epithelial miR-223 suppressed neutrophil wound response and NF-B activation in the basal epithelial cells. Together, our data provide the mechanism of the multifaceted role of miR-223 and highlight the previously overlooked relevance of epithelial cells in miR-223 related diseases.
2017-02-17 | GSE94996 | GEO
Project description:We used a multi-omics approach combining transcriptomics, proteomics and metabolomics to study the impact of over-expression and inhibition of the microRNA miR-223, a pleiotropic regulator of metabolic-related disease, in the RAW monocyte-macrophage cell line. We analyzed the levels of proteins, mRNAs, and metabolites in order to identify genes involved in miR-223 regulation, to determine candidate disease biomarkers and potential therapeutic targets. We observed that both up- and down-regulation of miR-223 induced profound changes in the mRNA, protein and metabolite profiles in RAW cells. Microarray-based transcriptomics evidenced a change in 120 genes that were linked predominantly to histone acetylation, bone remodeling and RNA regulation. In addition, 30 out the 120 genes encoded long noncoding RNAs. The nanoLC-MS/MS revealed that 52 proteins were significantly altered when comparing scramble, pre- and anti-miR-223 treatments. Sixteen out of the mRNAs coding these proteins genes are predicted to have binding sites for miR-223. CARM-1, Ube2g2, Cactin and Ndufaf4 were confirmed to be miR-223 targets by western blotting. Analyses using Gene Ontology annotations evidenced association with cell death, splicing and stability of mRNAs, bone remodeling and cell metabolism. miR-223 alteration changed the expression of CARM-1, Ube2g2, Cactin and Ndufaf4 during osteoclastogenesis and macrophage, indicating that these genes are potential biomarkers of these processes. The most important discriminant metabolites found in the metabolomics study were found to be hydrophilic amino acids, carboxylic acids linked to metabolism and pyrimidine nucleotides, indicating that changes in miR-223 expression alter the metabolic profile of cells, and may affect their apoptotic and proliferative state.
2021-03-29 | PXD009844 | Pride
Project description:Acute lung injury (ALI) is characterized by acute respiratory failure in the setting of non-cardiogenic pulmonary edema, causing acute respiratory distress syndrome (ARDS) in patients and contributes significantly to mortality of critically illness. The main goal of our study is to elucidate the role of miRNAs in neutrophil-epithelial communication during pulmonary inflammation and thereby identifying novel targets for therapy of acute lung injury (ALI). In our studies we identified a miR-223-dependent neutrophil-epithelial crosstalk during ALI. Activated neutrophils (PMN) and pulmonary epithelial cells come into a close spatial relationship during ALI. And, since previous studies had indicated the possibility that inflammatory cell-dependent release of miRNA-containing microvesicles could function as a means of exchanging genetic information from a donor to a target cell, we assessed PMN-elicited alterations of pulmonary epithelial miRNA expression in an experimental co-culture setup. This approach provided a selective and extremely robust readout: While other miRNAs were not or only moderately altered in their expression, pulmonary-epithelial-expressed miR-223 was significantly induced after 4 or 6h of co-incubation. Additional in vitro and in vivo studies clearly demonstrate that this increase of epithelial miR-223 is not due to miR-223 transcriptional induction, but instead PMN-dependent and caused by shuttling miR-223 from PMN into pulmonary epithelial cells. To address the functional role of miR-223-dependent neutrophil-epithelial crosstalk during ALI, we exposed mice to ventilator-induced ALI and observed robust induction of pulmonary miR-223 during ALI, while increases of miR-223 were completely abolished after antibody-depletion of PMN. Moreover, studies of alveolar epithelial cells isolated from mice with ALI showed robust increases of miR-223, indicating that miR-223 is shuttled from PMN towards alveolar epithelia during ALI in vivo. Functional studies revealed that gene-targeted mice for miR-223 experience a more severe phenotype during ALI as compared to controls, while their phenotype could be resuscitated by nanoparticle-mediated overexpression of miR-223 in the lungs. In summary, these studies reveal a novel role of miR-223-dependent neutrophil-epithelial crosstalk representing an anti-inflammatory pathway that can be targeted for ALI treatment.
2015-09-30 | GSE47625 | GEO
Project description:Severe acute respiratory syndrome coronavirus (SARS-CoV) and the closely related SARS-CoV-2 are emergent highly pathogenic human respiratory viruses causing acute lethal disease associated with lung damage and dysregulated inflammatory responses. SARS-CoV envelope protein (E) is a virulence factor involved in the activation of various inflammatory pathways. Here, we study the contribution of host miRNAs to the virulence mediated by E protein. Small RNAseq analysis of infected mouse lungs identified miRNA-223 as a potential regulator of pulmonary inflammation, since it was significantly increased in SARS-CoV-WT virulent infection as compared to the attenuated SARS-CoV-∆E infection. In vivo inhibition of miRNA-223-3p increased mRNA levels of pro-inflammatory cytokines and NLRP3 inflammasome, suggesting that during lung infection, miRNA-223 might contribute to restrict an excessive inflammatory response. Interestingly, miRNA-223-3p inhibition also increased the levels of the CFTR transporter, which is involved in edema resolution and was significantly downregulated in the lungs of mice infected with the virulent SARS-CoV-WT virus. At the histopathological level, a decrease in the pulmonary edema was observed when miR-223-3p was inhibited, suggesting that miRNA-223-3p was involved in the regulation of the SARS-CoV-induced inflammatory pathology. These results indicate that miRNA-223 participates in the regulation of E protein mediated- inflammatory response during SARS-CoV infection by targeting different host mRNAs involved in the pulmonary inflammation and identify miRNA-223 as a potential therapeutic target in SARS-CoV infection.
2022-02-04 | GSE180563 | GEO
Project description:Here, we found that microRNA-223 (miR-223) was highly elevated in hepatocytes after high fat diet (HFD) feeding in mice and in human nonalcoholic steatohepatitis (NASH) samples. Genetic deletion of the miR-223 induced a full spectrum of nonalcoholic fatty liver disease (NAFLD) in mice after long-term (up to one year) HFD feeding including NASH-related steatosis, inflammation, fibrosis and HCC. To better explore the mechanisms underlying the abnormalities observed in HFD-fed miR-223KO mice, we examined hepatic gene expression in 3-month-HFD-fed WT and miR-223KO mice by microarray analysis. Finally, we revealed that miR-223 plays a key role in controlling steatosis-to-NASH progression by inhibiting hepatic Cxcl10 and Taz expression.
2019-03-30 | GSE129080 | GEO
Project description:Gene expression profiling of bone marrow derived eosinophils from miR-223 wildtype or miR-223 deficient mice
2012-08-25 | E-MEXP-3350 | biostudies-arrayexpress
Project description:miR-223 is step-wise increasingly up-regulated in the normal esophagus - Barrett's esophagus -esophageal adenocarcinoma carcinoma sequence. In this study, we aimed to determine the function of miR-223 in esophageal adenocarcinoma carcinogenesis.
2013-02-07 | GSE44120 | GEO
Project description:miR-223 is step-wise increasingly up-regulated in the normal esophagus - Barrett's esophagus -esophageal adenocarcinoma carcinoma sequence. In this study, we aimed to determine the function of miR-223 in esophageal adenocarcinoma carcinogenesis. miR-223 was transfected in OE33 cells using 10nM pre-miR hsa-miR-223 miRNA precursor (Ambion, Life Technologies, Grand Island, NY) and lipofectamin 2000 (OE33_223_1 and OE33_223_2). Mock control OE33 cells were transfected with a negative control pre-miR miRNA (OE33_NEG_1 and OE33_NEG_2). HumanHT-12 v4 Expression BeadChip arrays (Illumina, San Diego, CA) were used for microarray hybridizations to examine the global gene expression of two biological replicated experiments (four samples in total). The array targets more than 25,000 annotated genes with 47,323 unique probes derived from the National Center for Biotechnology Information (NCBI) Reference Sequence (RefSeq) Release 38 and UniGene (Build 199) databases.
2013-02-07 | E-GEOD-44120 | biostudies-arrayexpress
Project description:Diabetes mellitus (DM) is a complex metabolic disorder. Long-term hyperglycemia may induce diabetic keratopathy (DK), which is mainly characterized by delayed corneal epithelial regeneration. MicroRNAs (miRNAs) have been reported to play regulatory roles during tissue regeneration. However, the molecular mechanism by which miRNAs influence epithelial regeneration in DK is largely unknown. In this study, we performed miRNA and mRNA sequencing of regenerative corneal epithelium tissue from streptozotocin-induced type 1 diabetic (T1DM) and wild-type mice to screen for differentially expressed miRNAs and mRNAs. Based on regulatory network analysis, miR-223-5p was selected for subsequent experiments and Hpgds was then identified as a direct target gene. MiR-223-5p downregulation significantly promoted diabetic corneal epithelial wound healing and nerve regeneration. However, the beneficial effects of miR-223-5p inhibition were abolished by an Hpgds inhibitor. Furthermore, mechanistic studies demonstrated that miR-223-5p suppression ameliorated inflammation and enhanced cell proliferation signaling in DK. Taken together, our findings revealed that the regulatory role of miR-223-5p in diabetic corneal epithelial and nerve regeneration by mediating inflammatory processes and cell proliferation signaling. And silencing miR-223-5p may contribute to the development of potential therapeutic strategies for DK.
2021-08-23 | GSE180493 | GEO