Project description:Expression profiling of human myositis muscle samples This study was designed to compare expression signatures among the various types of inflammatory myopathy, dermatomyositis (DM), inclusion body myositis (IBM), necrotizing myopathy (NM), nonspecific myopathy (NS), and polymyositis (PM) compared to normal (NL) muscle.
Project description:Juvenile dermatomyositis (JDM), the most common pediatric inflammatory myopathy, is a systemic vasculopathy affecting young children. Epidemiology studies documenting an antecedent illness in the 3 mo before the first definite symptom (rash and/or weakness) of JDM are supported by immunologic data that suggest that the disease pathophysiology is Ag driven. The purpose of this study was to compare the gene expression profiles in muscle biopsies of four untreated DQA1*0501(+) JDM children with profiles from children with a known necrotizing myopathy (Duchenne muscular dystrophy), as well as an in vitro antiviral model (NF90), and healthy pediatric controls. Nearly half (47%) of the dysregulated genes in JDM were associated with the immune response. In particular, increased expression of IFN-alphabeta-inducible genes 6-16, myxovirus resistance protein p78, latent cytosolic transcription factor, LMP2, and TAP1 was observed. This profile is consistent with an IFN-alphabeta transcription cascade seen in the in vitro viral resistance model. The IFN-alphabeta-inducible profile was superimposed on transcription profiles reflective of myofiber necrosis and regeneration shared with Duchenne muscular dystrophy. Expressed genes were confirmed by quantitative real-time PCR (6-16), immunofluorescence (thrombospondin 4), and immunolocalization (IFN-gamma, p21). Keywords: other
Project description:Atrial fibrillation is associated with stuctural remodelling of the atria that involves various cell types, including cardiac myocytes, endothelial cells, and immune cells. Atrial myopathy forms the substrate for an increased risk for AF onset and on the other hand AF drives atrial myopathy. Atrial myopathy is linked to risk factors such as aging, hypertension, obesity, or heart failure. Aldosterone and the mineralocorticoid receptor are drivers of pathological remodeling in atrial myopathy. In this study, we investigated the effect of aldosterone on left atrial gene expression and cell-cell communication.
Project description:Complement proteins are deposited in the muscles of patients with myositis. However, the local expression and regulation of complement genes within myositis muscle have not been well characterized. In this study, bulk RNA sequencing (RNAseq) analyses of muscle biopsy specimens revealed that complement genes are locally overexpressed and correlate with markers of myositis disease activity, including the expression of interferon-gamma (IFN )-induced genes. Single cell and single nuclei RNAseq analyses showed that most local expression of complement genes occurs in macrophages, fibroblasts, and satellite cells, with each cell type expressing different sets of complement genes. Biopsies from immune-mediated necrotizing myopathy patients, who have the lowest levels of IFN -induced genes, also had the lowest complement gene expression levels. Furthermore, data from cultured human cells showed that IFN upregulates complement expression in macrophages, fibroblasts, and muscle cells. Taken together, our results suggest that in myositis muscle, IFN coordinates the local overexpression of complement genes that occurs in several cell types.
Project description:We performed microarray analysis on ISCU myopathy patient muscle biopsies to identify transcriptional modulation of pathways involved in the cellular response to Fe-S cluster deficiency. We included RNA samples from five healthy control individuals as well as three different ISCU myopathy patients.
Project description:To elucidate the regulating networks of dysregulated ncRNAs in Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) with m.A3243G mutation.
Project description:To elucidate the regulating networks of dysregulated ncRNAs in Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) with m.A3243G mutation.