Project description:Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and highly lethal lung disease with unknown etiology and poor prognosis.
Project description:Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing lung disease that is difficult to diagnose and follows an unpredictable clinical course. The object of this study was to develop a predictive gene signature model of IPF from whole lung tissue. We collected whole lung samples from 11 IPF patients undergoing diagnostic surgical biopsy or transplantation. Whenever possible, samples were obtained from different lobes. Normals consisted of healthy organs donated for transplantation. We measured gene expression on microarrays. Data were analyzed by hierarchical clustering and Principal Component Analysis. By this approach, we found that gene expression was similar in the upper and lower lobes of individuals with IPF. We also found that biopsied and explanted specimens contained different patterns of gene expression; therefore, we analyzed biopsies and explants separately. Signatures were derived by fitting top genes to a Bayesian probit regression model. We developed a 153-gene signature that discriminates IPF biopsies from normal. We also developed a 70-gene signature that discriminates IPF explants from normal. Both signatures were validated on an independent cohort. The IPF Biopsy signature correctly diagnosed 76% of the validation cases (p < 0.01), while IPF Explant correctly diagnosed 78% (p < 0.001). Examination of differentially expressed genes revealed partial overlap between IPF Biopsy and IPF Explant and almost no overlap with previously reported IPF gene lists. However, several overlapping genes may provide a basis for developing therapeutic targets. 17 samples from 11 patients with IPF (6 patients provided a pair of samples from upper and lower lobes; 5 patients contributed singleton samples); 6 control specimens were obtained from routine lung volume reduction of healthy donor lungs at the time of lung transplantation.
Project description:Idiopathic pulmonary fibrosis (IPF), a chronic progressive lung disease of unknown etiology, is characterized by the expansion of myofibroblasts and abnormal deposition of extracellular matrix in the lung parenchyma. To elucidate the molecular mechanisms that lead to IPF, we analyzed myofibroblasts established from patients with IPF by oligonucleotide microarrays. Gene expression profiles revealed a novel pathophysiologic function of myofibroblasts as a generator of reactive oxygen species, and a self-defense mechanism against oxidative stress of their own generating. Experiment Overall Design: We isolated two myofibroblast cell culture from patients with idiopathic pulmonary fibrosis. Embryonic pulmonary fibroblast was used for the reference.
Project description:We aimed at characterizing disease-specific differences by comparing the transcriptomes of epithelial cells (ECs) from idiopathic pulmonary fibrosis (IPF) and non-IPF sources
Project description:Idiopathic pulmonary fibrosis (IPF) is an untreatable fibrotic lung disease characterized by fibroblast proliferation and epithelial mesenchymal transition. Using miRNA expression microarrays we identified 96 differentially expressed miRNA in IPF lungs which included let-7d, miR-30 family, miR-29 family and miR-154 family. Lung tissue samples for microarray analysis were obtained through the University of Pittsburgh Health Sciences Tissue Bank. 13 samples were obtained from surgical remnants of biopsies or lungs explanted from patients with IPF who underwent pulmonary transplant, and 12 control normal lung tissues obtained from the disease free margins with normal histology of lung cancer resection specimens. The morphologic diagnosis of IPF was based on typical microscopic findings consistent with usual interstitial pneumonia. Total RNA was labeled with Cy3 and hybridized on Agilent 8X15K microRNA array (Agilent Technologies, Santa Clara, CA). After 20 hours hybridization, arrays were washed and scanned according to the manufacturer’s protocol.
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.