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| Status |
Public on Aug 09, 2018 |
| Title |
FOXF1 inhibits pulmonary fibrosis by preventing CDH2-CDH11 cadherin switch in myofibroblasts |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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.
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| Overall design |
RNA from fibroblasts isolated from bleomycin-treated Foxf1fl/fl and myoFoxf1 KO mouse lungs
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| Contributor(s) |
Black M, Du Y, Xu Y, Kalinichenko VV, V Kalin T |
| Citation(s) |
29642003 |
| |
| Submission date |
Feb 09, 2018 |
| Last update date |
Mar 21, 2019 |
| Contact name |
Yan Xu |
| E-mail(s) |
[email protected]
|
| Organization name |
Cicinnati children's Hospital Medical Center
|
| Department |
Pulmonary Biology
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| Street address |
3333 Burnet Avenue
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| City |
Cincinnati |
| State/province |
Ohio |
| ZIP/Postal code |
45229 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA433652 |
| SRA |
SRP132579 |
