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Charaterization of monocytes/macrophages function in Club cell regeneration after naphthalene injury in WT mice

ABSTRACT: Charaterization of monocytes/macrophages function in Club cell regeneration after naphthalene injury in WT mice

PROVIDER: PRJNA649517 | ENA |

REPOSITORIES: ENA

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Depletion of club cells attenuates bleomycin-induced lung injury and fibrosis in mice

Project description:Background and objective: The role of bronchiolar epithelial cells in the pathogenesis of pulmonary fibrosis has not been addressed. We previously demonstrated that DNA damage was found in bronchiole at early phase, and subsequently extended to alveolar cells at later phase in bleomycin-induced pulmonary fibrosis in mice. Club cells are progenitor cells for bronchiole, and are recognized to play protective roles against lung inflammation and damage. The aim of the study was to elucidate the role of club cells in the development of pulmonary fibrosis. Methods: C57BL/6J mice were received naphthalene intraperitoneally at day -2 to deplete club cells, and were given intratracheal bleomycin or vehicle at day 0. Lung tissues were obtained at day 1, 7, and 14, and bronchoalveolar lavage was performed at day 14. Gene expression was analysed from bronchiolar ephithelial cells sampled by laser captured microdissection at day 14. Results: Surprisingly, naphthalene-induced club cell depletion protected mice from bleomycin-induced lung injury and fibrosis. We conclude that club cells are involved in the development of lung injury and fibrosis.

2017-02-08 | GSE94522 | GEO

Charaterization of function of ST2 receptor on macrophages function during Club cell regeneration after naphthalene injury in WT mice

Project description:Charaterization of function of ST2 receptor on macrophages function during Club cell regeneration after naphthalene injury in WT mice

| PRJNA649519 | ENA

Bronchiolar progenitors and club cells in mouse lung

Project description:Gene expression patterns of bronchiolar progenitors and club cells in mouse lung were examined by microarray experiments. Although it has not yet been fully characterized, a subset of epithelial cells lining bronchioles are best understood as bronchiolar progenitors that self-renew over the long term and that can differentiate into more differentiated club cells and ciliated cells. The bronchiolar progenitors are distinct from club cells and characteristically express the alveolar type 2 cell marker, prosurfactant protein C, with lower levels of club cell secretory protein/Scgb1a1. There are also functional differences between them; while club cells can be depleted by naphthalene because of the abundance of cytochrome P450 enzyme Cyp2f2, bronchiolar progenitors are resistant to naphthalene-induced depletion because of defects in the enzyme.

2016-02-17 | E-MTAB-4460 | biostudies-arrayexpress

Involvement of Igf1r in Bronchiolar Epithelial Regeneration: Role During Repair Kinetics after Selective Club Cell Ablation

Project description:Regeneration of lung epithelium is vital for maintaining airway function and integrity. An imbalance between epithelial damage and repair is at the basis of numerous chronic lung diseases such as asthma, COPD, pulmonary fibrosis and lung cancer. IGF (Insulin-like Growth Factors) signaling has been associated with most of these respiratory pathologies, although their mechanisms of action in this tissue remain poorly understood. Expression profiles analyses of IGF system genes performed in mouse lung support their functional implication in pulmonary ontogeny. Immuno-localization revealed high expression levels of Igf1r (Insulin-like Growth Factor 1 Receptor) in lung epithelial cells, alveolar macrophages and smooth muscle. To further understand the role of Igf1r in pulmonary homeostasis, two distinct lung epithelial-specific Igf1r mutant mice were generated and studied. The lack of Igf1r disturbed airway epithelial differentiation in adult mice revealed enhanced proliferation and altered morphology in distal airway club cells. During recovery after naphthalene-induced club cell injury, the kinetics of terminal bronchiolar epithelium regeneration was hindered in Igf1r mutants, revealing increased proliferation and delayed differentiation of club and ciliated cells. Amid airway restoration, lungs of Igf1r deficient mice showed increased levels of Igf1, Insr, Igfbp3 and epithelial precursor markers, reduced amounts of Scgb1a1 protein, and alterations in IGF signaling mediators. These results support the role of Igf1r in controlling the kinetics of cell proliferation and differentiation during pulmonary airway epithelial regeneration after injury.

2017-02-09 | GSE88836 | GEO

Single cell transcriptome analysis of adult murine lung airway epithelium after NAPH-induced injury

Project description:To comprehensively study how club cells response to airway epithelial injury, we performed single cell transcriptomic analysis of the normal and NAPH injured lung samples. Our analysis reveals that a previously undescribed pathway promoting mucous metaplasia that involves VEGFa and its receptor KDR. Our single cell RNA sequencing analysis revealed that VEGFR2 (also known as FLK1 or KDR) is expressed in club cell subpopulations. Loss of KDR, its ligand VEGFa, or downstream MEK/ERK causes excessive differentiation of club cells into mucous cells (mainly goblet cells) during development and regeneration following Naphthalene (NAPH) challenge.

2021-04-07 | GSE171571 | GEO

C/EBPa Regulates Protease/anti-protease Balance and Mediates Bronchiolar Cell Recovery After Injury

Project description:In the present study, we hypothesized that C/EBPa (CCAAT/enhancer-binding protein alpha) plays a role in cell regeneration in response to bronchiolar epithelial cell injury. C/EBPa mediated ciliated cell regeneration after naphthalene bronchiolar epithelial cell injury in vivo. Furthermore, we demonstrated that C/EBPa regulates protease/anti-protease balance after lung injury, and intratracheal treatment with anti-protease (BPTI) restored ciliated cell regeneration after naphthalene injury in CebpaD/D mice. Cebpa d/d VS. Control mice 0hr, 3hr and 72hr after naphthalene injury. Three replicates each.

2012-05-12 | E-GEOD-29285 | biostudies-arrayexpress

C/EBPa Regulates Protease/anti-protease Balance and Mediates Bronchiolar Cell Recovery After Injury

2012-05-13 | GSE29285 | GEO

Charaterization of function of ST2 receptor on macrophages function during Club cell regeneration after naphthalene injury in WT mice

Project description:During repair phase after naphathalene injury 3 subsets of myeloid cells accumulate at the site of injury including P1 (monoyte), P2 (monocyte-derived macrophages and P3 (resident alternatively activated airway macrophages). ST2 receptor was found to be expressed by P2 and P3 subsets. To understand which biological processes in lung macrophages were regulated by ST2, myeloid cell subsets were flow-sorted from Naphthalene-treated WT and ST2-/- mice on d6 and their transcriptome analyzed using RNA-seq

2020-07-30 | GSE155359 | GEO

Club cells employ regeneration mechanisms during lung tumorigenesis

Project description:Club cells employ regeneration mechanisms during lung tumorigenesis

| PRJNA735231 | ENA

Club cells employ regeneration mechanisms during lung tumorigenesis

Project description:Club cells employ regeneration mechanisms during lung tumorigenesis

| PRJNA735233 | ENA