Idiopathic pulmonary fibrosis: aberrant recapitulation of developmental programs?
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ABSTRACT:
SUBMITTER: Selman M
PROVIDER: S-EPMC2265304 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We previously identified a novel molecular subtype of idiopathic pulmonary fibrosis (IPF) defined by increased expression of cilium-associated genes, airway mucin gene MUC5B, and KRT5 marker of basal cell airway progenitors. Here we show the association of MUC5B and cilia gene expression in human IPF airway epithelial cells, providing further rationale for examining the role of cilium genes in the pathogenesis of IPF. We demonstrate increased multiciliogenesis and changes in motile cilia structure of multiciliated cells both in IPF and bleomycin lung fibrosis models. Importantly, conditional deletion of a cilium gene, Ift88 (intraflagellar transport 88), in Krt5 basal cells reduces Krt5 pod formation and lung fibrosis, whereas no changes are observed in Ift88 conditional deletion in club cell progenitors. Our findings indicate that aberrant injury-activated primary ciliogenesis and Hedgehog signaling may play a causative role in Krt5 pod formation, which leads to aberrant multiciliogenesis and lung fibrosis. This implies that modulating cilium gene expression in Krt5 cell progenitors is a potential therapeutic target for IPF.
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Project description:Global mRNA expression was compared between stable and progressive IPF using bronchoalveolar lavage derived mesenchymal stromal cells
2017-01-10 | GSE73854 | GEO
Project description:BACKGROUND: Idiopathic pulmonary fibrosis (IPF) and pulmonary sarcoidosis are typical interstitial lung diseases with unknown etiology that cause lethal lung damages. There are notable differences between these two pulmonary disorders, although they do share some similarities. Gene expression profiles have been reported independently, but differences on the transcriptional level between these two entities have not been investigated. METHODS/RESULTS: All expression data of lung tissue samples for IPF and sarcoidosis were from published datasets in the Gene Expression Omnibus (GEO) repository. After cross platform normalization, the merged sample data were grouped together and were subjected to statistical analysis for finding discriminate genes. Gene enrichments with their corresponding functions were analyzed by the online analysis engine "Database for Annotation, Visualization and Integrated Discovery" (DAVID) 6.7, and genes interactions and functional networks were further analyzed by STRING 9.0 and Cytoscape 3.0.0 Beta1. One hundred and thirty signature genes could potentially differentiate one disease state from another. Compared with normal lung tissue, tissue affected by IPF and sarcoidosis displayed similar signatures that concentrated on proliferation and differentiation. Distinctly expressed genes that could distinguish IPF from sarcoidosis are more enriched in processes of cilium biogenesis or degradation and regulating T cell activations. Key discriminative network modules involve aspects of bone morphogenetic protein receptor two (BMPR2) related and v-myb myeloblastosis viral oncogene (MYB) related proliferation. CONCLUSIONS: This study is the first attempt to examine the transcriptional regulation of IPF and sarcoidosis across different studies based on different working platforms. Groups of significant genes were found to clearly distinguish one condition from the other. While IPF and sarcoidosis share notable similarities in cell proliferation, differentiation and migration, remarkable differences between the diseases were found at the transcription level, suggesting that the two diseases are regulated by overlapping yet distinctive transcriptional networks.
| S-EPMC3743918 | biostudies-literature
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.
2023-01-01 | GSE195770 | GEO
Project description:Idiopathic pulmonary fibrosis (IPF)
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Project description:BackgroundThe multidimensional and complex care needs of patients with idiopathic pulmonary fibrosis (IPF) call for appropriate care models. This systematic review aimed to identify care models or components thereof that have been developed for patients with IPF in the outpatient clinical care, to describe their characteristics from the perspective of chronic integrated care and to describe their outcomes.MethodsA systematic review was conducted using state-of-the-art methodology with searches in PubMed/Medline, Embase, CINAHL and Web Of Science. Researchers independently selected studies and collected data, which were described according to the Chronic Care Model (CCM).ResultsEighteen articles were included describing 13 new care models or components. The most commonly described CCM elements were 'delivery system design' (77%) and 'self-management support' (69%), with emphasis on team-based and multidisciplinary care provision and education. The most frequently described outcome was health-related quality of life.ConclusionsGiven the high need for integrated care and the scarcity and heterogeneity of data, developing, evaluating and implementing new models of care for patients with IPF and the comprehensive reporting of these endeavours should be a priority for research and clinical care.
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Project description:Cellular plasticity and de-differentiation are hallmarks of tissue/organ regenerative capacity in diverse species. Despite a more restricted capacity for regeneration, humans with age-related chronic diseases, such as cancer and fibrosis, show evidence of a recapitulation of developmental gene programs. We have previously identified a resident population of mesenchymal stromal cells (MSCs) in the terminal airways-alveoli by bronchoalveolar lavage (BAL) of human adult lungs. In this study, we characterized MSCs from BAL of patients with stable and progressive idiopathic pulmonary fibrosis (IPF), defined as <5% and ≥10% decline, respectively, in forced vital capacity over the preceding 6-month period. Gene expression profiles of MSCs from IPF subjects with progressive disease were enriched for genes regulating lung development. Most notably, genes regulating early tissue patterning and branching morphogenesis were differentially regulated. Network interactive modeling of a set of these genes indicated central roles for TGF-β and SHH signaling. Importantly, fibroblast growth factor-10 (FGF-10) was markedly suppressed in IPF subjects with progressive disease, and both TGF-β1 and SHH signaling were identified as critical mediators of this effect in MSCs. These findings support the concept of developmental gene re-activation in IPF, and FGF-10 deficiency as a potentially critical factor in disease progression.
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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.
2020-05-13 | PXD010965 | Pride
Project description:Idiopathic pulmonary fibrosis (IPF) is a chronic and ultimately fatal disease in which an impaired healing response to recurrent micro-injuries is thought to lead to fibrosis. Recent findings hint at a role for B cells and autoimmunity in IPF pathogenesis. We previously reported that circulating B cells from a fraction of patients, compared with healthy controls, express increased levels of the signaling molecule Bruton's tyrosine kinase (BTK). However, it remains unclear whether B cell receptor (BCR) signaling is altered in IPF. Here, we show that the response to BCR stimulation is enhanced in peripheral blood B cells from treatment-naïve IPF patients. We observed increased anti-immunoglobulin-induced phosphorylation of BTK and its substrate phospholipase Cγ2 (PLCγ2) in naïve but not in memory B cells of patients with IPF. In naïve B cells of IPF patients enhanced BCR signaling correlated with surface expression of transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) but not B cell activating factor receptor (BAFFR), both of which provide pro-survival signals. Interestingly, treatment of IPF patients with nintedanib, a tyrosine kinase inhibitor with anti-fibrotic and anti-inflammatory activity, induced substantial changes in BCR signaling. These findings support the involvement of B cells in IPF pathogenesis and suggest that targeting BCR signaling has potential value as a treatment option.
| S-EPMC8226954 | biostudies-literature
Project description:Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and highly lethal lung disease with unknown etiology and poor prognosis.
2019-05-29 | GSE116086 | GEO