Project description:RNA expression profiling was carried out for systemic sclerosis (scleroderma) on skin biopsies obtained from both diffuse scleroderma (dcSSc) and limited scleroderma (lcSSc) subjects patients and compared to normal subjects. The patient group comprised of 4 dcSSc and 2 lcSSc subjects, all of whom were Caucasian and belonged to the age range of 42-73 (Mean age = 61.6). Patient sample set consisted of 3 females and 3 males. Race matched female volunteers from the same geographical area were recruited as controls (n = 4) and belonged to the age range of 41-62 (Mean age = 52).
Project description:Fibroblast were isolated from either back or forearm punch biopsies taken by Dr. Kari Connolly(UCSF) from either normal control patients, patients with a diagnosis of Systemic Sclerosis with Diffuse Scleroderma and patients with a diagnosis of morphea. Scleroderma fibroblast were grown to confluence, media was changed and the RNA prepared from the cells 48 hrs later (to avoid serum responsive genes). A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Keywords: disease_state_design
Project description:Fibroblast were isolated from either back or forearm punch biopsies taken by Dr. Kari Connolly(UCSF) from either normal control patients, patients with a diagnosis of Systemic Sclerosis with Diffuse Scleroderma and patients with a diagnosis of morphea. Scleroderma fibroblast were grown to confluence, media was changed and the RNA prepared from the cells 48 hrs later (to avoid serum responsive genes). A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. User Defined
Project description:Scleroderma is a complex autoimmune disease characterized by abnormal fibroblast proliferation and excessive collagen deposits in the skin and internal organs. We previously showed that esomeprazole, an FDA-approved drug for gastric disorders, may prevent dermal fibrosis. Here, we demonstrate that esomeprazole exerts anti-proliferative effects on scleroderma fibroblasts by interfering with cell cycle regulation. To test this, we evaluated the antiproliferative effect of esomeprazole and the underlying molecular mechanisms using primary fibroblasts derived from patients with scleroderma. BrdU incorporation, flow cytometry, immunofluorescence, Western blot analysis, RNA sequencing, and functional enrichment analysis all showed a decrease in fibroblast proliferation. In addition, esomeprazole inhibited the proliferation of scleroderma fibroblasts in a dose-dependent manner, as measured by the Ki-67 marker. Intriguingly, esomeprazole arrested fibroblasts in the G1 phase of the cell cycle, resulting in a reduction of cells in the S phase. Expression of p21, a known inhibitor of cyclin-dependent kinases (CDKs), was elevated, while CDK1 and CDK2 levels decreased following esomeprazole treatment. These data provide important insights into how esomeprazole regulates fibroblast proliferation in scleroderma and suggest that it may represent a potential therapeutic intervention for scleroderma.
Project description:This SuperSeries is composed of the following subset Series: GSE3886: Scleroderma Morphea Normal Fibroblasts GSE3887: Scleroderma Architecture Cell Lines Abstract: We used DNA microarrays representing >12,000 human genes to characterize gene expression patterns in skin biopsies from individuals with a diagnosis of systemic sclerosis with diffuse scleroderma. We found consistent differences in the patterns of gene expression between skin biopsies from individuals with scleroderma and those from normal, unaffected individuals. The biopsies from affected individuals showed nearly indistinguishable patterns of gene expression in clinically affected and clinically unaffected tissue, even though these were clearly distinguishable from the patterns found in similar tissue from unaffected individuals. Genes characteristically expressed in endothelial cells, B lymphocytes, and fibroblasts showed differential expression between scleroderma and normal biopsies. Analysis of lymphocyte populations in scleroderma skin biopsies by immunohistochemistry suggest the B lymphocyte signature observed on our arrays is from CD20+ B cells. These results provide evidence that scleroderma has systemic manifestations that affect multiple cell types and suggests genes that could be used as potential markers for the disease Refer to individual Series
Project description:This SuperSeries is composed of the following subset Series: GSE17914: IL13 and CCL2 Drive Disease in an Inflammatory Subset of Scleroderma [cGVHD] GSE24403: IL13 and CCL2 drive disease in an inflammatory subset of Scleroderma [IL13] GSE24409: IL13 and CCL2 drive disease in an inflammatory subset of Scleroderma [IL4] Refer to individual Series