Transcriptomics

Dataset Information

8

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


ABSTRACT: 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

ORGANISM(S): Homo sapiens  

SUBMITTER: K Lebrigand   I Henaoui  P Barbry  Kevin Lebrigand  L Plantier  B Mari 

PROVIDER: E-GEOD-52612 | ArrayExpress | 2014-10-01

SECONDARY ACCESSION(S): GSE52612PRJNA229476

REPOSITORIES: GEO, ArrayExpress

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Publications

Forkhead Box F1 represses cell growth and inhibits COL1 and ARPC2 expression in lung fibroblasts in vitro.

Melboucy-Belkhir Sara S   Pradère Pauline P   Tadbiri Sara S   Habib Stéfanie S   Bacrot Antoine A   Brayer Stéphanie S   Mari Bernard B   Besnard Valérie V   Mailleux Arnaud A   Guenther Andreas A   Castier Yves Y   Mal Hervé H   Crestani Bruno B   Plantier Laurent L  

American journal of physiology. Lung cellular and molecular physiology 20140926 11


Aberrant expression of master phenotype regulators or alterations in their downstream pathways in 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 u  ...[more]

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