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Series GSE123726 Query DataSets for GSE123726
Status Public on Feb 05, 2019
Title The Forkhead Box F1 Transcription Factor Inhibits Collagen Deposition and Accumulation of Myofibroblasts During Liver Fibrosis
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Hepatic fibrosis is the common end stage to a variety of chronic liver injuries and is characterized by an excessive deposition of extracellular matrix (ECM), which disrupts the liver architecture and impairs liver function. The fibrous lesions are produced by myofibroblasts, which differentiate from hepatic stellate cells (HSC). The myofibroblasts transcriptional networks remain poorly characterized. Previous studies have shown that the Forkhead box F1 (FOXF1) transcription factor is expressed in HSCs and stimulates their activation during acute liver injury; however, the role of FOXF1 in the progression of hepatic fibrosis is unknown. In the present study, we generated αSMACreER;Foxf1fl/fl mice to conditionally inactivate Foxf1 in myofibroblasts during carbon tetrachloride-mediated liver fibrosis. Foxf1 deletion increased collagen depositions and disrupted liver architecture. Timp2 expression was significantly increased in Foxf1-deficient mice while MMP9 activity was reduced. RNA sequencing of purified liver myofibroblasts demonstrated that FOXF1 inhibits expression of pro-fibrotic genes, Col1α2, Col5α2, and Mmp2 in fibrotic livers and binds to active repressors located in promotors and introns of these genes. Overexpression of FOXF1 inhibits Col1a2, Col5a2, and MMP2 in primary murine HSCs in vitro. Altogether, FOXF1 prevents aberrant ECM depositions during hepatic fibrosis by repressing pro-fibrotic gene transcription in myofibroblasts and HSCs.
 
Overall design RNAseq on isolated hepatic stromal cells from Foxf1 fl/fl and αSMACreER;Foxf1 fl/fl mice after 5 weeks of carbon tetrachloride-induced liver injury.
 
Contributor(s) Flood HM, Dasgupta N, Kalinichenko VV
Citation(s) 30670377
Submission date Dec 12, 2018
Last update date Mar 19, 2019
Contact name Hannah M Flood
Organization name CCHMC
Department Department of Pediatrics
Lab Kalinichenko Lab
Street address 3333 Burnet Ave
City Cincinnati
State/province OH
ZIP/Postal code 45229
Country USA
 
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (2)
GSM3510182 Foxf1 fl/fl (Wild-type)
GSM3510183 αSMACreER;Foxf1 fl/fl (Knockout)
Relations
BioProject PRJNA509647
SRA SRP173338

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE123726_RAW.tar 1.4 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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