Project description:Comparison of the gene expression profile in lungs from dogs with spontaneous canine idiopathic pulmonary fibrosis and from control dogs with histologically normal lungs.
Project description:We used the scRNA-seq to characterize disease-related heterogeneity within cell populations of macrophages/monocytes in the bronchoalveolar lavage fluid from West Highland white terriers either healthy or affected with canine idioapthic pulmonary fibrosis. The disease is still not well understood, occurs in old West Highland white terriers and results from deposition of fibrotic tissue in the lung parenchyma causing respiratory failure.
Project description:Pulmonary fibrosis (PF) is associated with many chronic lung diseases including Systemic sclerosis (SSc), Idiopathic Pulmonary Fibrosis (IPF) and Cystic Fibrosis (CF) which are characterized by the progressive accumulation of stromal cells and formation of scar tissue. Pulmonary fibrosis is a dysregulated response to alveolar injury which causes a progressive decline in lung function and refractory to current pharmacological therapies. Airway and alveolar epithelial cells and stromal cells contribute to pulmonary fibrosis but the cell-specific pathways and gene networks that are responsible for the pathophysiology are unknown. Recent animals models generated in our lab demonstrate clinical phenotypes seen in human fibrotic disease. The mouse model of transforming growth factor-? (TGF?)-induced fibrosis include conditionally expressing TGF? in the lung epithelium under control of the CCSP promoter driving rtTA expression (CCSP/TGF?). This allow the TGF? is only expressed in airway and alveolar epithelial cells and only when mice fed doxycycline (Dox). Similar to PF in humans, TGF? mice on Dox developed a progressive and extensive adventitial, interstitial and pleural fibrosis with a decline in lung mechanics. Thus, the TGF? transgenic mouse is a powerful model to determine lung cell-specific molecular signatures involved in pulmonary fibrosis. In this study, we sought to determine changes in the transcriptome during TGF?-induced pulmonary fibrosis. Our results showed that several pro-fibrotic genes increased in the lungs of TGF? mice. This study demonstrates that WT1 network gene changes associated with fibrosis and myfibroblast accumulation and thus may serve as a critical regulator fibrotic lung disease. mRNA profiles of CCSP/- and CCSP/TGFalpha mice treated with Dox
Project description:Idiopathic pulmonary fibrosis (IPF) is an untreatable fibrotic lung disease characterized by fibroblast proliferation and epithelial mesenchymal transition.miRNA let-7d and mir30b were found to be signifcantly down regulated in IPF. Compared to control we over expressed these miRNAs in Human Fetal Lung Fibroblast cell line
Project description:Idiopathic pulmonary fibrosis (IPF) is an incurable lung disease with a poor prognosis. Fibroblasts and myofibroblasts are the key cells in the fibrotic process. Pirfenidone was approved as an anti-fibrotic drug for IPF treatment as it is able to slow disease progression. The mechanisms by which the drug acts on fibroblasts are not clear. Therefore, this study aims to examine the effects of pirfenidone on the human lung fibroblast (HLF) transcriptome in vitro.
Project description:Healthy donor and idiopathic pulmonary fibrosis (IPF) patient lung tissues were digested, Lin–EpCAM+ cells were isolated with FACS, and then single-cell RNA-seq was performed.
Project description:Idiopathic pulmonary fibrosis (IPF) is a lethal fibrotic lung condition with an unpredictable disease course. The pathology of IPF starts in the lung bases such that a patient’s lung apices are comparatively less fibrotic at the time of transplantation. We hypothesized that RNA sequencing of the lung apices and bases may identify differentially expressed genes that better reflect disease progression in IPF. Samples were derived from both right and left lungs when available and RNA Seq was performed on a total of 139 samples.
Project description:The response to a 4 hour treatment with TGFbeta (4 ng/ml) was evaluated in lung fibroblasts derived from three controls (normal periphery of resected tumor), open lung biopsies from three patients with idiopathic pulmonary fibrosis (usual interstitial pneumonia pattern on biopsy) and from three patients with fibrosing alveolitis associated with systemic sclerosis (fibrotic non specific interstitial pneumonia pattern on biopsy). Lung fibroblasts were grown to confluence in DMEM with 10% fetal calf serum. At confluence, lung fibroblasts were serum-deprived overnight, and exposed to either 4 ng/ml of activated TGF-Ã1 (R&D Systems) or serum-free culture medium with 0.1% BSA for four hours.
