Select correlative genes involved in pathogenesis of idiopathic interstitial pneumonia by high-throughput sequencing analysis
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ABSTRACT: We report abonormally expressed genes of idiopathic interstitial pneumonia by RNA-seq analysis. BMP3 was found down-regulated in idiopathic intestital pneumonia patients, and it closely correlated with pathogenesis of disease. The role of BMP3 in advancement of idiopathic interstitial pneumonia was verified by a series of experiments. Examination of differentially expressed genes in idiopathic interstitial pneumonia. Verification the function of selected gene in pathogenesis of idiopathic interstitial pneumonia in vivo and invitro.
Project description:We report abonormally expressed genes of idiopathic interstitial pneumonia by RNA-seq analysis. BMP3 was found down-regulated in idiopathic intestital pneumonia patients, and it closely correlated with pathogenesis of disease. The role of BMP3 in advancement of idiopathic interstitial pneumonia was verified by a series of experiments.
Project description:This study aimed to delineate molecular phenotypes of the lung microenvironment across idiopathic interestitial pneumonias, namely interstitial pneumonia with autoimmune features (IPAF)and idiopathic pulmonary fibrosis (IPF) through proteomic analysis of bronchoalveolar lavage fluid (BALF).
Project description:Acute Interstitial Pneumonia (AIP) represents a severe form of diffuse lung injury within the idiopathic interstitial pneumonia spectrum. Given the limited understanding of its molecular basis, this study aims to elucidate AIP's transcriptomic profiles to uncover its pathophysiological underpinnings and identify potential therapeutic targets.
Project description:Idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP) are the 2 most common forms of idiopathic interstitial pneumonia. Response to therapy and prognosis are remarkably different. The clinical-radiographic distinction between IPF and NSIP may be challenging. We sought to investigate the gene expression profile of IPF vs. NSIP We used microarray to identifiy the gene expression profiles in patients with IPF and NSIP, mixed IPF/NSIP histologic pattern and normal controls.
Project description:Rationale: Idiopathic interstitial pneumonia (IIP) and its’ familial variants are progressive and largely untreatable disorders with poorly understood molecular mechanisms. Both the genetics and the histologic type of IIP play a role in understanding the etiology and pathogenesis of interstitial lung disease, but transcriptional signatures of these subtypes are unknown. Objectives: To evaluate gene expression in the lung tissue from patients with usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP) that were either familial or non-familial in origin and compare them to gene expression from normal lung parenchyma. Methods: We profiled RNA from lungs of 16 patients with sporadic IIP, 10 with familial IIP, and 9 normal controls on a whole human genome oligonucleotide microarray. Results: Significant transcriptional differences exist in familial and sporadic IIPs. The genes distinguishing the genetic subtypes belong to the same functional categories as transcripts that distinguish IIP from normal samples. Relevant categories include chemokines and growth factors and their receptors, complement components, genes associated with cell proliferation and death, and genes in the Wnt pathway. Keywords: disease state analysis
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.
Project description:Chronic fibrosing idiopathic interstitial pneumonia (IIP) is characterized by alveolar epithelial damage, activation of fibroblast proliferation, and loss of normal pulmonary architecture and function. This analysis was performed to investigate the genetic backgrounds of IIP and identify potential biomarkers that can aid in diagnosis and serve as novel therapeutic target.
Project description:The mechanisms and molecular pathways underlying interstitial lung diseases (ILDs) are poorly understood. Systems biology approaches were used to identify perturbed networks in these disease states to gain a better understanding of the underlying mechanisms of disease. Through profiling genes and miRNAs, we found subsets of genes and miRNAs that distinguish different disease stages, ILDs from controls, and idiopathic pulmonary fibrosis (IPF) from non-specific interstitial pneumonitis (NSIP). Traditional pathway analysis revealed several disease-associated modules involving genes from the TGF-beta, Wnt, focal adhesion and smooth muscle actin pathways that may be involved in advancing fibrosis. A comprehensively integrative approach was used to construct a global gene regulatory network based on the perturbation of key regulatory elements, transcriptional factors and miRNAs. The data also demonstrated that several subnetworks were significantly associated with key molecules involved in the diseases. We present a broad overview of the disease at a molecular level and discuss several possibly key regulatory molecular circuits that could play central roles in facilitating the progression of ILDs. Lung tissue samples from 23 patients with IPF or related disorders were obtained from the Lung Tissue Research Consortium (www.ltrcpublic.org). 11 samples came from patients who had been diagnosed with usual interstitial pneumonia/ idiopathic pulmonary fibrosis (UIP/IPF), 5 samples came from patients with non-specific interstitial pneumonia (NSIP), the remaining from patients with uncharacterized fibrosis and from patients with other ILD variants. B. Biopsies from uninvolved lung tissue from lung cancer patients (5 samples) and from one lung transplant patient were used as controls for comparison with the ILD samples.