Project description:Idiopathic pulmonary fibrosis (IPF) is characterized by pathogenic accumulation of scar tissue in the lung. Many of the processes implicated in fibrosis also occur following pneuomonectomy, but fibrotic changes are absent. We aimed to characterize differences between the responses to pneumonectomy and bleomycin, a fibrosis-inducing drug. We identified Itpkc as a gene uniquely up-regulated following pneumonectomy and identified it to have anti-fibrotic effects in cell culture. We then used RNA-sequencing on normal human lung fibroblasts overexpressing ITPKC or control to gain a deeper understanding of its role.
Project description:RNA expression profiling was performed on normal human lung fibroblast WI38 cells following overexpression of p53 and pRb, in order to identify genes co-regulated and involved in mediating p53 and pRb tumor suppressor processes.
Project description:We have found through previous experiments that circCUL2 acts as a key regulator of cancer-associated fibroblasts activation. To determine how circCUL2 exert its function, we performed mRNA sequencing of normal fibroblasts (NFs) and circCUL2-transduced NFs. 48 hours after transfection, RNA was isolated and sent for total RNA sequencing. Differential gene expression between circCUL2-overexpression and empty vector revealed enrichment for several inflammation pathways implicating involvement of these pathways in inflammatory cancer-associated fibroblasts activation.
Project description:There is increasing evidence for a crucial contribution of the tumor microenvironment to cancer development and progression since several stromal components, including fibroblasts, interact with cancer cells regulating their behavior and ultimately affecting tumor phenotype. To investigate the cross-talk between cancer cells and lung-derived fibroblasts we have prospectively collected surgical specimens of lung cancer and normal lung tissue and established primary fibroblast cultures from different areas of the lungs. We have generated cultures from cancer specimens (Cancer Associated Fibroblasts, CAF) and cultures from normal lung tissue either proximal (Adjacent Fibroblasts, AF) or distant from the neoplastic lesion (Normal fibroblasts, NF). Gene and miRNA expression profiles were obtained from 60 cultures to identify fibroblast properties related to cancer progression.
Project description:Pulmonary fibrosis develops as a consequence of environmentally induced lung injury and/or an inherent disease susceptibility causing fibroblast activation, proliferation and extracellular matrix deposition. The study was undertaken to characterise global gene expression in pulmonary fibroblasts to better understand the mechanisms underlying the fibrotic fibroblast phenotype. Gene expression was evaluated in lung fibroblasts derived from ten controls (normal periphery of resected tumor), open lung biopsies from eight patients with interstitial lung disease associated with systemic sclerosis (fibrotic non specific interstitial pneumonia pattern on biopsy), and from three patients with usual interstitial pneumonia. Lung fibroblasts were grown to confluence in DMEM with 10% fetal calf serum. At confluence, lung fibroblasts were serum-deprived for 44 hours in the presence of fibroblast growth medium with the addition of 0.1% bovine serum albumin (Sigma).