Project description:NSAID-exacerbated respiratory disease (N-ERD) represents a particularly severe endotype of chronic rhinosinusitis with nasal polyps (CRSwNP), which affects around 10-16% of CRSwNP patients. N-ERD is characterized by severe and refractory nasal polyposis, bronchial asthma and intolerance to non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin. Today, the pathogenesis of N-ERD remains incompletely understood and curative treatments are lacking. Using a global transcriptomic approach, we identified local changes between the mucosa of N-ERD nasal polyps and healthy control inferior turbinates. Nasal brushing samples were collected from inferior turbinates of healthy controls and nasal polyps of N-ERD patients under anterior rhinoscopy and stored at -80°C in RNAprotect until RNA isolation and RNAseq.
Project description:Age-related hearing (ARHL) loss affects a large part of the human population with a major impact on our aging societies. Yet, underlying mechanisms are not understood, and no validated therapy or prevention exists. NADPH oxidases (NOX), are important sources of reactive oxygen species (ROS) in the cochlea and might therefore be involved in the pathogenesis of ARHL. Here we investigate ARHL in a mouse model. Wild type mice showed early loss of hearing and cochlear integrity, while animals deficient in the NOX subunit p22phox remained unaffected up to six months. Genes of the excitatory pathway were down-regulated in p22phox-deficient auditory neurons. Our results demonstrate that NOX activity leads to upregulation of genes of the excitatory pathway, to excitotoxic cochlear damage, and ultimately to ARHL. In the absence of functional NOXs, aging mice conserve hearing and cochlear morphology. Our study offers new insights into pathomechanisms and future therapeutic targets of ARHL.
Project description:Fibrotic changes in the myocardium and cardiac arrhythmias represent fatal complications in rheumatic disease systemic sclerosis (SSc), however the underlying mechanisms remain elusive. Fos-related antigen-2 (Fosl-2) has been implicated in development of organ fibrosis. Mice overexpressing Fosl-2 (Fosl-2tg) showed interstitial cardiac fibrosis, disorganized connexin43/40 in intercalated discs and deregulated expression of genes controlling conduction system. Fosl-2tg mice developed higher heart rate (HR), prolonged QT intervals, arrhythmias with prevalence of premature ventricular contractions, ventricular tachycardias, II-degree atrio-ventricular blocks and reduced HR variability. Following stimulation with isoproterenol Fosl-2tg mice showed impaired HR response. To assess the role of inflammation in cardiac fibrosis we used Rag2-/-Fosl-2tg mice lacking T/B cells. These mice showed no myocardial fibrosis and ECG abnormalities. Transcriptomics analysis of cardiac Rag-2-/-Fosl-2wt/Rag2-/-Fosl-2tg/Fosl-2tg fibroblasts revealed that systemic inflammation triggered fibrotic and arrhythmogenic alterations while Fosl-2-overexpression mediated profibrotic signature. In human cardiac fibroblasts FOSL-2-overexpression enhanced myofibroblast signature under proinflammatory or profibrotic stimuli. These results demonstrate that under immunofibrotic conditions activator protein 1 transcription factor component Fosl-2 exaggerates myocardial fibrosis, arrhythmias and aberrant response to stress.
Project description:To determine changes in pancreatic mesenchymal cells during embryonic development, we analyzed the transcriptome of these cells at three embryonic days: 13.5 ('L1'), 15.5 ('L2'), and 17.5 ('L3'). Pancreatic mesenchymal cells were isolated by FACS from Nkx3.2-Cre;LSL-YFP pancreatic tissues based on these cells fluorescent labeling. Two groups of mice were analyzed for each embryonic day ('P1', 'P2').
Project description:We have got a yellow shell variety of Pinctada fucata martensii after years of artificial breeding. To identify differentially expressed genes between yellow shell and normal black shell pearl oysters, we performed label-free proteomic analyses by LC-MS using mantle edge tissues.
Project description:NSAID-exacerbated respiratory disease (N-ERD) represents a particularly severe endotype of chronic rhinosinusitis with nasal polyps (CRSwNP), which affects around 10-16% of CRSwNP patients. N-ERD is characterized by severe and refractory nasal polyposis, bronchial asthma and intolerance to non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin. Today, the pathogenesis of N-ERD remains incompletely understood and curative treatments are lacking. Macrophages are important source and target cells of arachidonic acid metabolites during type 2 inflammation, that have been neglected in N-ERD pathogenesis despite their presence in the nasal mucosa of N-ERD patients. Using a global transcriptomic approach, we identified systemic and local changes in macrophages between N-ERD patients and healthy controls. We isolated macrophages from induced sputum (sMac) and compared them to 7-days in vitro-differentiated, alveolar-like monocyte-derived macrophages (aMDM). Cells were lysed in RLT buffer with 1% beta-mercaptoethanol and stored at -80°C until RNA isolation and RNAseq. Since sMac yield of healthy controls was low, we pooled RNA of three donors (= sample S1) but excluded the data from subsequent analyses. Thus Analysis 1 shows the intra-group comparison of N-ERD sMac vs. N-ERD aMDM. In a second analysis (Analysis 2), we compared N-ERD aMDM vs. healthy control aMDM for transcriptome differences present in monocyte (blood)-derived cells.
Project description:In this study the root transcriptome profiles of young seedlings (5 days after germination at 23C) of two tomato species differing in cold tolerance were analysed and compared after a subsequent treatment for 3 days at 23 or 15C by RNAseq. Aim was to elucidate molecular mechanisms underlying root development associated with suboptimal-temperature tolerance during early seedling establishment.