Lung endothelial cells regulate pulmonary fibrosis through FOXF1/R-Ras signaling (Human).
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA878787 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Lung endothelial cells regulate pulmonary fibrosis through FOXF1/R-Ras signaling
| PRJNA878780 | ENA
Project description:Pulmonary fibrosis results from dysregulated repair of damaged tissue caused by persistent injury of lung epithelium. Multiple cell types in the lung are involved in the process of repair. During lung fibrogenesis, normal endothelial cells (EC) are re-programmed into fibrosis-associated EC. Transcriptional factors that control re-programming are poorly understood. Using single cell RNA-sequencing of EC from donor and idiopathic pulmonary fibrosis (IPF) lungs, and lungs from bleomycin-treated mice, we identified endothelial transcription factors (TF) that were differentially expressed during fibrosis. Focusing on one of endothelial TF, FOXF1, we demonstrated that FOXF1 is decreased in EC within human IPF and mouse bleomycin-injured fibrotic lungs.
2022-09-16 | GSE213017 | GEO
Project description:Pulmonary fibrosis results from dysregulated repair of damaged tissue caused by persistent injury of lung epithelium. Multiple cell types in the lung are involved in the process of repair. During lung fibrogenesis, normal endothelial cells (EC) are re-programmed into fibrosis-associated EC. Transcriptional factors that control re-programming are poorly understood. Using single cell RNA-sequencing of EC from donor and idiopathic pulmonary fibrosis (IPF) lungs, and lungs from bleomycin-treated mice, we identified endothelial transcription factors (TF) that were differentially expressed during fibrosis. Focusing on one of endothelial TF, FOXF1, we demonstrated that FOXF1 is decreased in EC within human IPF and mouse bleomycin-injured fibrotic lungs.
2022-09-16 | GSE213016 | GEO
Project description:Pulmonary fibrosis results from dysregulated repair of damaged tissue caused by persistent injury of lung epithelium. Multiple cell types in the lung are involved in the process of repair. During lung fibrogenesis, normal endothelial cells (EC) are re-programmed into fibrosis-associated EC. Transcriptional factors that control re-programming are poorly understood. Using single cell RNA-sequencing of EC from donor and idiopathic pulmonary fibrosis (IPF) lungs, and lungs from bleomycin-treated mice, we identified endothelial transcription factors (TF) that were differentially expressed during fibrosis. Focusing on one of endothelial TF, FOXF1, we demonstrated that FOXF1 is decreased in EC within human IPF and mouse bleomycin-injured fibrotic lungs.
2022-09-16 | GSE213279 | GEO
Project description:Lung endothelial cells regulate pulmonary fibrosis through FOXF1/R-Ras signaling (Mouse II).
| PRJNA880322 | ENA
Project description:Lung endothelial cells regulate pulmonary fibrosis through FOXF1/R-Ras signaling (Mouse I).
| PRJNA878788 | ENA
Project description:Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant accumulation of collagen-secreting myofibroblasts. Development of effective therapies is limited due to incomplete understanding of molecular mechanisms regulating myofibroblast expansion. FOXF1 transcription factor is expressed in resident lung fibroblasts, but its role in lung fibrosis remains unknown due to the lack of genetic mouse models. Through comprehensive analysis of human IPF genomics data, lung biopsies and transgenic mice with fibroblast-specific inactivation of FOXF1, the present study shows that FOXF1 inhibits pulmonary fibrosis. FOXF1 deletion increases myofibroblast invasion, collagen secretion, and promotes a switch from of N-cadherin (CDH2) to Cadherin-11 (CDH11), which is critical step in acquisition of pro-fibrotic phenotype. FOXF1 directly binds to Cdh2 and Cdh11 promoters and differentially regulates transcription of these genes. Re-expression of CDH2 or inhibition of CDH11 in FOXF1-deficient cells reduces myofibroblast invasion in vitro. FOXF1 inhibits pulmonary fibrosis by regulating a switch from CDH2 to CDH11 in lung myofibroblasts.
2018-08-09 | GSE110408 | GEO
Project description:The Forkhead Box f1 (Foxf1) transcriptional factor (previously known as HFH-8 or Freac-1) is expressed in endothelial and smooth muscle cells in the embryonic and adult lung. To assess effects of Foxf1 during lung injury, we used CCl4 injury model. Foxf1+/- mice developed severe airway obstruction and bronchial edema, associated with increased numbers of pulmonary mast cells and increased mast cell degranulation following injury. Pulmonary inflammation in Foxf1+/- mice was associated with diminished expression of Foxf1, increased mast cell tryptase and increased expression of CXCL12, the latter being essential for mast cell migration and chemotaxis. Foxf1 haploinsufficiency caused pulmonary mastocytosis and enhanced pulmonary inflammation following chemically-induced lung injury, indicating an important role for Foxf1 in the pathogenesis of pulmonary inflammatory responses. Keywords: Influence of genetic modification on the pulmonary inflamation Foxf1+/- mice in which the Foxf1 allele was disrupted by an in-frame insertion of a nuclear localizing -galactosidase (-Gal) gene were bred for ten generations into the Black Swiss mouse genetic background. Carbon tetrachloride (CCl4; Sigma, St Louis, MO) was dissolved in mineral oil at a 1:20 ratio v/v and a single intraperitoneal (i.p.) injection of CCl4 (0.5 l of CCl4/ 1g of body weight) was administered to male Foxf1+/- mice or their wild type (WT) littermates as described.
2008-09-04 | E-GEOD-11112 | biostudies-arrayexpress
Project description:The Forkhead Box f1 (Foxf1) transcriptional factor (previously known as HFH-8 or Freac-1) is expressed in endothelial and smooth muscle cells in the embryonic and adult lung. To assess effects of Foxf1 during lung injury, we used CCl4 injury model. Foxf1+/- mice developed severe airway obstruction and bronchial edema, associated with increased numbers of pulmonary mast cells and increased mast cell degranulation following injury. Pulmonary inflammation in Foxf1+/- mice was associated with diminished expression of Foxf1, increased mast cell tryptase and increased expression of CXCL12, the latter being essential for mast cell migration and chemotaxis. Foxf1 haploinsufficiency caused pulmonary mastocytosis and enhanced pulmonary inflammation following chemically-induced lung injury, indicating an important role for Foxf1 in the pathogenesis of pulmonary inflammatory responses. Keywords: Influence of genetic modification on the pulmonary inflamation
2008-09-04 | GSE11112 | GEO
Project description:Pulmonary fibrosis results from dysregulated lung repair and involves multiple cell types. The role of endothelial cells (EC) in lung fibrosis is poorly understood. Using single cell RNA-sequencing we identified endothelial transcription factors involved in lung fibrogenesis, including FOXF1, SMAD6, ETV6 and LEF1. Focusing on FOXF1, we found that FOXF1 is decreased in EC within human idiopathic pulmonary fibrosis (IPF) and mouse bleomycin-injured lungs. Endothelial-specific Foxf1 inhibition in mice increased collagen depositions, promoted lung inflammation, and impaired R-Ras signaling. In vitro, FOXF1-deficient EC increased proliferation, invasion and activation of human lung fibroblasts, and stimulated macrophage migration by secreting IL-6, TNFα, CCL2 and CXCL1. FOXF1 inhibited TNFα and CCL2 through direct transcriptional activation of Rras gene promoter. Transgenic overexpression or endothelial-specific nanoparticle delivery of Foxf1 cDNA decreased pulmonary fibrosis in bleomycin-injured mice. Nanoparticle delivery of FOXF1 cDNA can be considered for future therapies in IPF.
| S-EPMC10156846 | biostudies-literature