Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA191030 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:MiR-155 promotes blood-brain barrier dysfunction in neuroinflammation (part 2)
| PRJNA191031 | ENA
Project description:MiR-155 promotes blood-brain barrier dysfunction in neuroinflammation
| PRJNA191023 | ENA
Project description:MicroRNA (miRNA)-mediated mRNA regulation directs many homeostatic and pathological processes, but how miRNAs coordinate aberrant esophageal inflammation during eosinophilic esophagitis (EoE) is poorly understood. Here, we report a deregulatory axis where microRNA-155 (miR-155) regulates epithelial barrier dysfunction by selectively constraining tight junction CLDN7 (claudin-7). MiR-155 is elevated in the esophageal epithelium of biopsies from patients with active EoE and in cell culture models. miR-155 localisation using in situ hybridisation (ISH) in patient biopsies, and intra-epithelial compartmentalisation of miR-155 shows expression predominantly within the basal epithelia. Epithelial miR-155 activity was evident through diminished target gene expression in 3D organotypic cultures, particularly in relatively undifferentiated basal cell states. Mechanistically, generation of a novel cell line with enhanced epithelial miR-155 stable overexpression induced a functionally deficient epithelial barrier in 3D air-liquid interface epithelial cultures measured by transepithelial electrical resistance (TEER). Histological assessment of 3D esophageal organoid cultures overexpressing miR-155 showed notable dilated intra-epithelial spaces. Unbiased RNA-sequencing analysis and immunofluorescence determined a defect in epithelial barrier tight junctions and revealed a selective reduction in the expression of critical esophageal tight junction molecule, claudin-7. Together, our data reveal a previously unappreciated role for miR-155 in mediating epithelial barrier dysfunction in esophageal inflammation.
2023-12-12 | GSE244629 | GEO
Project description:Electronic cigarette exposure disrupts blood-brain barrier integrity, promotes neuroinflammation, and leads to cognitive dysfunction
| PRJNA596914 | ENA
Project description:Over-expression of miR-155 induces changes in the pattern of gene expression of hCMEC/D3 cells. hypothesis tested in the present study was that miR-155 constitute an important regulatory control of the brain endothelial response to inflammatory cytokines. To identify miR-155 target genes in brain endothelim that might be implicated in BBB dysfunction relevant to human disease, we then analysed changes in mRNA expression of hCMEC/D3 cells that overexpress miR-155 and results were contrasted to cells transfected with scrambled miR. To ectopically express miR-155 in hCMEC/D3 cells, 30 nM of pre-miR-155 and the siPORT Amine transfection agent (Applied Biosystems, Warrington, UK) were combined following the manufacturerM-bM-^@M-^Ys instructions.
2014-04-29 | E-GEOD-44693 | biostudies-arrayexpress
Project description:Brain aging is associated with neurovascular uncoupling, blood-brain barrier (BBB) dysfunction, neuroinflammation, and cognitive decline. Brain endothelial cells are essential for maintaining BBB integrity and neurovascular homeostasis and are enriched for the transcription factor Krüppel-like factor 4 (KLF4). Because endothelial KLF4 expression declines with aging, we investigated whether endothelial KLF4 depletion contributes to age-associated neurovascular dysfunction and neuropsychiatric impairment.
2026-05-28 | GSE333394 | GEO
Project description:Brain aging is associated with neurovascular uncoupling, blood-brain barrier (BBB) dysfunction, neuroinflammation, and cognitive decline. Brain endothelial cells are essential for maintaining BBB integrity and neurovascular homeostasis and are enriched for the transcription factor Krüppel-like factor 4 (KLF4). Because endothelial KLF4 expression declines with aging, we investigated whether endothelial KLF4 depletion contributes to age-associated neurovascular dysfunction and neuropsychiatric impairment.
2026-05-28 | GSE333397 | GEO
Project description:Disruption of the blood-brain barrier (BBB) and increased vascular leakage contribute to neuroinflammation in Alzheimer’s disease (AD), driving disease pathogenesis and progression. However, the mechanisms underlying BBB dysfunction and neuroinflammation in AD remain unclear. Angiopoietin-2 (ANGPT2), a ligand for the TIE2 receptor, is known to destabilize blood vessels and compromise vascular integrity under inflammatory conditions. To investigate the role of ANGPT2 in AD pathology, we overexpressed ANGPT2 specifically in brain endothelial cells using an adeno-associated virus (AAV) system in 5xFAD transgenic mice. Single-nucleus RNA sequencing (snRNA-seq) revealed distinct transcriptional changes associated with ANGPT2 overexpression, pointing to multiple pathways through which ANGPT2 may exacerbate AD progression. These findings identify ANGPT2 as a key driver of BBB dysfunction and neuroinflammation in AD, highlighting it as a potential therapeutic target for mitigating disease progression.
2026-04-15 | GSE286360 | GEO
Project description:Background: Mitochondrial dysfunction is closely related to ischemic brain injury. Increased expression of dynamin-related protein 1 (Drp1) in neuronal cells plays a crucial role in ischemia/hypoxia-induced mitochondrial damage, and dysregulation of miR-155 expression is implicated in cerebral ischemic injury. However, the mechanistic link between miR-155 dysregulation and Drp1-mediated mitochondrial damage in ischemic/hypoxic neuronal cells remains largely elusive. Methods: Oxygen-glucose deprivation (OGD)-treated Neuro-2a cells were employed to investigate the effects of hypoxia/ischemia on miR-155 expression. The cells transfected with miR-155 mimic and miR-155 inhibitor were used to clarify the the role of miR-155 in OGD-induced mitochondrial damage. The expression levels of PGC-1α, PPARα, PPARβ/δ, PPARγ, ERRα, and Drp1 were assessed using qRT-PCR, Western blotting, and immunofluorescence staining, and their interactions were identified by confocal colocalization and co-immunoprecipitation experiments. Mitochondrial functions were evaluated by measuring ATP content, ROS, MMP, and mPTP opening. Chromatin immunoprecipitation (ChIP) assay was performed to detect the binding of ERRα to the Drp1 promoter. Results: miR-155 expression in OGD-treated neuronal cells exhibited a significant upregulation in a time-dependent manner. Elevated miR-155 induced excessive mitochondrial fission and dysfunction, as evidenced by a decreased ATP content, increased ROS generation, depolarized MMP, and mPTP opening, which is accompanied by a markedly reduced expression of PPAR family members, particularly the PPARγ. Mechanistically, miR-155 weakened the interaction between PGC-1α and PPARγ by suppressing their expressions and thus downregulated ERRα expression, which prevents the binding of ERRα to the Drp1 promoter, thereby relieving the repression of the Drp1 promoter by ERRα. These findings suggest that PGC-1α and ERRα negatively regulate Drp1 expression in neuronal cells. Notably, inhibition of miR-155 could ameliorate mitochondrial dysfunction by improving the OGD-induced dysregulation of PPARγ/PGC-1α/ERRα-Drp1 axis in Neuro-2a cells, providing new insights into the mechanisms of ischemia/hypoxia-induced mitochondrial dysfunction. Conclusion: Our findings reveal a novel mechanism by which miR-155 contributes to mitochondrial damage by driving the ischemia/hypoxia-induced dysregulation of PPARγ/PGC-1α/ERRα-Drp1 axis in neuronal cells, identifying potential new therapeutic targets for the treatment of post-ischemic mitochondrial damage.
2026-07-10 | GSE332777 | GEO
Project description:Intervertebral disc (IVD) herniation is a complex and multifactorial condition with challenging diagnosis and limited therapeutic options, highlighting the need for reliable biomarkers to improve clinical decision-making. The aim of this study was to identify circulating prognostic biomarkers of IVD herniation regression. The plasma proteomic profile and the expression of circulating non-coding RNAs wereas analysed in a rat model ofs subjected to IVD herniation and proteomic and miRNA levels were correlated to herni-ation size. Four candidate proteins were identified (TNC, COPS3, JUP, GNAI2) that were significantly correlated with herniation size, with TNC further validated by ELISA. Additionally, miR-143-3p, miR-10b-5p, miR-27a-3p, miR-140-5p, miR-155-5p, miR-146a-5p and miR-21-5p were positively correlated with herniation size. Moreover, TNC, COPS3, JUP and GNAI2 were found to be potentiala targets of miR-155-5p. TNC-miR-155-5p pro-tein-miRNA pair standout as promising candidates to be part of a putative regulatory module worth investigating as a prognostic tool. This study provides the first combined proteomic and miRNAs account of preclinical plasma biomarkers of IVD herniation size, where TNC-miR-155-5p emerge as promising elements of a regulatory module with IVD herniation prognostic potential.
2026-02-02 | PXD071649 | Pride