Project description:Idiopathic Pulmonary Fibrosis (IPF) is a chronic progressive lung disease that affects more than 5 million people worldwide with a steady increase in both incidence and mortality. There is currently no effective therapy and the median survival without transplant is 2-5 years. The etiological factor is unknown, but several observational and pathogenesis studies suggest that environmental agents may cause IPF. DNA methylation is a type of chemical modification of DNA such environmental and occupational factors, that can induced a changes in the regulation of biological processes and link to diseases such as a cancer. We hypothesize that the global changes in methylation patterns of IPF lungs caused by environmental factors. In this study we will identify the global methylation signatures of the IPF lung and to compare to methylation signature of lung cancer. The DNA methylation profiles of IPF lung tissue differs from control lung but it shares great similarity with that of lung cancer. Immunoprecipitated methylated DNA from 12 IPF lungs, 10 lung adenocarcinomas and 10 normal histology lungs obtained from the same group of adenocarcinoma patients was hybridized to Agilent human CpG Islands Microarrays. Only probes with a hybridization Tm value between 79 C and 93C were included in the analysis because these show higher quality signal. All probes were divided according to their Tm into 14 groups/bins differing by 1C. Probe signals in each bin were standardized to have an average of 0 and a standard deviation of 1. To work in a CpG island oriented manner, we scored each island for its likelihood to be methylated. For that purpose, each probe was mapped to the genome and the signals of the probes that were mapped to a single CpG island were averaged to obtain the islandM-bM-^@M-^Ys methylation score. Data analysis was performed using BRB-Array Tools and DAVID Bioinformatics Resources software packages.
Project description:Idiopathic Pulmonary Fibrosis (IPF) is a chronic progressive lung disease that affects more than 5 million people worldwide with a steady increase in both incidence and mortality. There is currently no effective therapy and the median survival without transplant is 2-5 years. The etiological factor is unknown, but several observational and pathogenesis studies suggest that environmental agents may cause IPF. DNA methylation is a type of chemical modification of DNA such environmental and occupational factors, that can induced a changes in the regulation of biological processes and link to diseases such as a cancer. We hypothesize that the global changes in methylation patterns of IPF lungs caused by environmental factors. In this study we will identify the global methylation signatures of the IPF lung and to compare to methylation signature of lung cancer. The DNA methylation profiles of IPF lung tissue differs from control lung but it shares great similarity with that of lung cancer.
Project description:Idiopathic pulmonary fibrosis (IPF) is a disease related to AT2 cell. We used flow cytometry to analyze the epithelial component of donor and IPF lungs. From the live cells, we first excluded the CD31PosCD45Pos and then selected the EPCAMPos cells for further analysis using the human AT2 cell marker HTll-280 and the surface marker PD-L1. Our data indicate that, the bona fide differentiated AT2 cells (HTll-280High PD-L1Neg), were drastically reduced in the context of IPF. More interestingly, the number of HTll-280Low/Neg PD-L1High was drastically increased, suggesting that HTll-280Low PD-L1High epithelial cells could represent a pool of progenitors linked to the deficient AT2 lineage. The aim of this experiment is further characterization of AT2 and PDL1+ cells in donor and IPF.
Project description:The aim of the current study is to find plasma-based biomarker candidates for Idiopathic Pulmonary Fibrosis (IPF). Incidence of IPF seems to be increasing in Europe and there is significant mortality associated with IPF. There are no sensistive biomarkers for IPF and diagnosis is entirely clinical and/or histopathological which is often delayed. Minimally invasive biomarkers of IPF would be expected to aid clinicians perfrom early diagnosis of IPF enabling better management of the disease.