Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

FOXF1 transcription factor promotes lung regeneration after partial pneumonectomy

ABSTRACT: FOXF1, a member of the forkhead box family of transcription factors, has been previously shown to be critical for lung development, homeostasis, and injury responses. However, the role of FOXF1 in lung regeneration is unknown. Herein, we performed partial pneumonectomy, a model of lung regeneration, in mice lacking one Foxf1 allele in endothelial cells (PDGFb-iCre/Foxf1fl/+ mice). Endothelial cell proliferation was significantly reduced in regenerating lungs from mice deficient for endothelial Foxf1. Decreased endothelial proliferation was associated with delayed lung regeneration as shown by reduced respiratory volume in Foxf1-deficient lungs. FACS-sorted endothelial cells isolated from regenerating PDGFb-iCre/Foxf1fl/+ and control lungs were used for RNAseq analysis to identify FOXF1 target genes. Foxf1 deficiency altered expression of numerous genes including those regulating extracellular matrix remodeling (Timp3, Adamts9) and cell cycle progression (Cdkn1a, Cdkn2b, Cenpj, Tubb4a), which are critical for lung regeneration. Deletion of Foxf1 increased Timp3 mRNA and protein, decreasing MMP14 activity in regenerating lungs. ChIPseq analysis for FOXF1 and histone methylation marks identified DNA regulatory regions with the Cd44, Cdkn1a, and Cdkn2b genes, indicating they are direct FOXF1 targets. Thus FOXF1 stimulates lung regeneration following partial pneumonectomy via direct transcriptional regulation of genes critical for extracellular matrix remodeling and cell cycle progression.

ORGANISM(S): Mus

PROVIDER: GSE100149 | GEO | 2017/09/12

SECONDARY ACCESSION(S): PRJNA390895

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Mus

Project description:FOXF1 transcription factor promotes lung regeneration after partial pneumonectomy

| PRJNA390895 | ENA

Lung endothelial cells regulate pulmonary fibrosis through FOXF1/R-Ras signaling (Mouse II).

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

Lung endothelial cells regulate pulmonary fibrosis through FOXF1/R-Ras signaling (Human).

2022-09-16 | GSE213017 | GEO

Lung endothelial cells regulate pulmonary fibrosis through FOXF1/R-Ras signaling (Mouse I).

2022-09-16 | GSE213016 | GEO

Decreases in adiponectin mediate inhibition of regenerative lung growth in obese mice

Project description:Obesity is associated with impairments of wound healing and tissue regeneration. Angiogenesis, the formation of new blood capillaries, plays a key role in organ regeneration and repair. Inhibition of lung angiogenesis impairs regenerative lung growth after unilateral pneumonectomy (PNX). However, the effects of obesity on post-PNX lung vascular and alveolar morphogenesis remain unclear. In this report, we have demonstrated that regenerative lung growth and angiogenic factor VEGFA expression induced by PNX are inhibited in Lepob/ob obese mice compared to Lepob/- mice. The levels of adiponectin, one of the adipokines that exhibits pro-angiogenic and vascular protective properties, increase in endothelial cells (ECs) isolated from remaining mouse lungs after unilateral PNX, while these effects are attenuated in Lepob/ob obese mice. Post-PNX lung growth, vascular and alveolar morphogenesis, and VEGFA levels in the lungs are inhibited in adiponectin knockout mice. Adiponectin agonist, AdipoRon stimulates post-PNX lung growth and vascular and alveolar morphogenesis in Lepob/ob obese mice. These findings suggest that obesity impairs lung vascular and alveolar regeneration and adiponectin may be one of the key molecules to improve lung regeneration in obese people.

2024-11-06 | GSE179227 | GEO

ROSA26Foxf1; Tie2-cre lung gene expression analysis.

Project description:Analysis of genes deregulated due to heterozygous overexpression of Foxf1 in endothelial and hematopoietic cells using Tie2-cre in embryonic day 18.5 mouse lungs. Total RNA obtained from three ROSA26Foxf1; Tie2-cre mouse lungs compared to three control ROSA26-lox-stop-lox (LSL) -Foxf1 mouse lungs.

2016-09-01 | E-GEOD-77881 | biostudies-arrayexpress

FOXF1 inhibits endothelial barrier function in the lung and transcriptionally activates the gene for the S1PR1 receptor

Project description:Multiple signaling pathways, structural proteins and transcription factors are involved in regulation of endothelial barrier function. The Forkhead protein FOXF1 is a key transcriptional regulator of lung embryonic development, and we use a conditional knockout approach to examine the role of FOXF1 in adult lung homeostasis and lung injury and repair. Tamoxifen-regulated deletion of both Foxf1 alleles in endothelial cells of adult mice (Pdgfb-iCreER/Foxf1 caused lung inflammation and edema, leading to respiratory insuffency and uniform mortality. Deletion of a single foxf1 allele was sufficient to increase susceptibility of heterozygous mice to acute lung injury. FOXF1 abundance was decreased in pulmonary endothelial cells of human patients with acute lung injury. Gene expression analysis of pulmonary endothelial cells of FOXF1 deletion indicated reduced expression for genes critical for maintance and regulation of adherens junctions. FOXF1 knockdown in vitro and in vivo disrupted adherens junctions, increased lung endothelial permeability, and the abundance of mRNA and protein for sphingosine 1 phosphate receptor 1 (S1PR1), a key regulator of endothelial barrier function. Chromatin immunoprecipitation and luciferase reporter assay demonstrated that FOXF1 directly bound to and induced the tanscriptional activity of the S1pr1 promoter. Pharmacological administratiion of S1P to injured pdgfb-iCreER/Foxf1 mice restored endothelial barrier function, decreased lung edema and improved survival. Thus, FOXF1 promotes normal lung homeostasis and lung repair, at least in part, by enhancing endothelial barrier function through transcriptional activation of the S1P/S1PR1/ signaling pathway.

2016-04-20 | GSE78184 | GEO

FOXF1 Promotes Tumor Vessel Normalization and Prevents Lung Cancer Progression through FZD4

Project description:Cancer cells re-program normal lung endothelial cells (EC) into tumor-associated endothelial cells (TEC) that form leaky vessels supporting carcinogenesis. Transcriptional regulators that control reprogramming of EC into TEC are poorly understood. We identified Forkhead box F1 (FOXF1) as a critical regulator of EC-to-TEC transition. FOXF1 was highly expressed in normal lung vasculature but was decreased in TEC within non-small cell lung cancers (NSCLC). Low FOXF1 correlated with poor overall survival of NSCLC patients. In mice, endothelial-specific deletion of FOXF1 decreased pericyte coverage, increased vessel permeability and hypoxia, and promoted lung tumor growth and metastasis. Endothelial-specific over-expression of FOXF1 normalized tumor vessels and inhibited progression of lung cancer. FOXF1-deficiency decreased Wnt/β-catenin signaling in TECs through direct transcriptional activation of Fzd4. Restoring FZD4 expression in FOXF1-deficient TECs through endothelial-specific nanoparticle delivery of Fzd4 cDNA rescued Wnt/β-catenin signaling in TECs, normalized tumor vessels and inhibited progression of lung cancer. Altogether, FOXF1 increases tumor vessel stability, and inhibits lung cancer progression by stimulating FZD4/Wnt/β-catenin signaling in TECs. Nanoparticle delivery of FZD4 cDNA has a promise for future therapies in NSCLC.

2024-03-09 | GSE255969 | GEO

Forkhead Box F1 (FOXF1) represses fibroblast functions relevant to fibrogenesis

Project description:Aberrant expression of master phenotype regulators by lung fibroblasts may play a central role in idiopathic pulmonary fibrosis (IPF). Interrogating IPF fibroblast transcriptome datasets, we identified Forkhead Box F1 (FOXF1), a DNA-binding protein required for lung development, as a candidate actor in IPF. Thus, we determined FOXF1 expression levels in fibroblasts cultured from normal or IPF lungs in vitro, and explored FOXF1 functions in these cells using transient and stable loss-of-function and gain-of-function models. FOXF1 mRNA and protein were expressed at higher levels in IPF compared with controls. In normal lung fibroblasts, FOXF1 repressed key fibroblast functions such as proliferation, survival, and expression of collagen-1 (COL1) and actin related protein 2/3 complex, subunit 2 (ARPC2). ARPC2 knockdown mimicked FOXF1 overexpression with regard to proliferation and COL1 expression. FOXF1 expression was induced by the antifibrotic mediator prostaglandin E2 (PGE2). Ex vivo, FOXF1 knockdown conferred CCL-210 lung fibroblasts the ability to implant and survive in uninjured mouse lungs. In IPF lung fibroblasts, FOXF1 regulated COL1 but not ARPC2 expression. In conclusion, FOXF1 functions and regulation were consistent with an antifibrotic role in lung fibroblasts. Higher FOXF1 levels in IPF fibroblasts may thus participate in a compensatory response to fibrogenesis. Lung fibroblasts derived from 4 different IPF patients (P313, P355, P375 and P426) were transiently transfected with pcfoxf1 or control pcDNA3.1-constructs. Total RNAs were extracted 24 h after transfection and hybridized on microarrays. One color experiment with 2 experimental conditions: pcfoxf1 and pcDNA3.1

2014-10-01 | E-GEOD-52612 | biostudies-arrayexpress

Forkhead Box F1 (FOXF1) represses fibroblast functions relevant to fibrogenesis

2014-10-01 | GSE52612 | GEO