Project description:Chronic rhinosinusitis without polyps (CRSsNP) is typified by inflammation of the sinonasal epithelium and the development of fibrosis. The precise pathophysiology of this common condition remains elusive. Here we aim to investigate the transcriptome (RNA transcripts in the cell) of the component nasal epithelial and fibroblast cells in CRSsNP and health to identify if there are clusters of differentially expressed genes as possible novel CRS therapeutic targets. Gene expression profiling by Illumina BeadArray of primary nasal epithelial and fibroblast cells in heatlh and chronic sinusitis. Samples from consenting human donors (Epithelial Case, n=13, Epithelial Control, n=11, Fibroblast Case, n=12, Fibroblast Control, n=12).
Project description:Chronic rhinosinusitis without polyps (CRSsNP) is typified by inflammation of the sinonasal epithelium and the development of fibrosis. The precise pathophysiology of this common condition remains elusive. Here we aim to investigate the transcriptome (RNA transcripts in the cell) of the component nasal epithelial and fibroblast cells in CRSsNP and health to identify if there are clusters of differentially expressed genes as possible novel CRS therapeutic targets.
Project description:We have sequenced miRNA libraries from human embryonic, neural and foetal mesenchymal stem cells. We report that the majority of miRNA genes encode mature isomers that vary in size by one or more bases at the 3’ and/or 5’ end of the miRNA. Northern blotting for individual miRNAs showed that the proportions of isomiRs expressed by a single miRNA gene often differ between cell and tissue types. IsomiRs were readily co-immunoprecipitated with Argonaute proteins in vivo and were active in luciferase assays, indicating that they are functional. Bioinformatics analysis predicts substantial differences in targeting between miRNAs with minor 5’ differences and in support of this we report that a 5’ isomiR-9-1 gained the ability to inhibit the expression of DNMT3B and NCAM2 but lost the ability to inhibit CDH1 in vitro. This result was confirmed by the use of isomiR-specific sponges. Our analysis of the miRGator database indicates that a small percentage of human miRNA genes express isomiRs as the dominant transcript in certain cell types and analysis of miRBase shows that 5’ isomiRs have replaced canonical miRNAs many times during evolution. This strongly indicates that isomiRs are of functional importance and have contributed to the evolution of miRNA genes
Project description:Aim of the work
1. To determine if chronic rhinosinusitis with nasal polyps’ (CRSwNP) populations are vitamin D deficient.
2. To determine the possible anti-inflammatory effect of vitamin D supplementation (clinically & histologically). & investigate its relation to immunohistochemical tissue expression of basic fibroblast growth factor
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:Chronic rhinosinusitis is classified into eosinophilic chronic rhinosinusitis (ECRS) and non-eosinophilic chronic rhinosinusitis (NECRS). ECRS is a refractory allergic disease involving a variety of immune and epithelial cells. S100A8 is a damage-associated molecular pattern that is closely related to allergic inflammation. However, the pathological implications of S100A8 in ECRS have not been clarified. We evaluated the role of S100A8 in the pathogenesis of ECRS. Gene expression profiles of nasal polyps obtained from patients with ECRS or NECRS were evaluated using RNA sequencing. S100A8 was identified as a significantly upregulated gene in nasal polyps associated with ECRS. Consistently, immunohistochemistry revealed that S100A8 stained intensely in nasal polyps from patients with ECRS. Human nasal epithelial cells expressed the receptor for advanced glycation end products and Toll-like receptor 4. Recombinant S100A8 protein induced interleukin-1β secretion in human nasal epithelial cells. Our data demonstrate that S100A8 induces production of interleukin-1β in the nasal epithelium, which may be involved in the pathogenesis of ECRS.