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Series GSE78853 Query DataSets for GSE78853
Status Public on Mar 02, 2017
Title Tricyclic Antidepressants Induce Inactivation of Hepatic Stellate Cell (HSC) Myofibroblasts
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Hepatic stellate cells (HSCs) are the primary cell type responsible for liver fibrosis, the final common pathway leading to cirrhosis and liver failure for nearly every cause of chronic liver disease. Activation of HSCs in response to injury represents the key step in hepatic fibrogenesis, and is characterized by a phenotypic change from a non-fibrogenic, quiescent HSC to a fibrogenic HSC myofibroblast that secretes extracellular matrix proteins responsible for the fibrotic scar. We developed a small molecule screen to identify compounds that revert fibrotic human HSC myofibroblasts to an inactive phenotype through the quantification of lipid droplets with fluorescent microscopy. Conditions were optimized in a 384-well format using culture in Matrigel as a positive control. We screened 1600 compounds and identified 30 small molecules that induce reversion to an inactive phenotype. Among the hits, we identified five tricyclic antidepressants (TCAs) and showed that this class of drugs also repressed ACTA2 and COL1A1 while promoting PPAR-gamma expression. RNA sequencing analysis implicated extracellular matrix proteins and the sphingolipid pathway as a target of the TCAs.
 
Overall design HSCs and HSCs stimulated with TGF-beta were treated with the TCA, nortriptyline or ethanol vehicle for 48 hours. RNA-seq was performed in duplicate for each condition
 
Contributor(s) Chen JY, Zhou C, Pondick JV, Mullen AC
Citation(s) 28322247, 35617485
Submission date Mar 02, 2016
Last update date Jun 01, 2022
Contact name Chan Zhou
E-mail(s) zhou.chan@mgh.harvard.edu
Phone 7062543741
Organization name Mass General Hospital, Harvard Medical School
Department gastroenterology
Lab Alan Mullen
Street address 55 Fruit Street
City Boston
State/province Massachusetts
ZIP/Postal code 02114
Country USA
 
Platforms (2)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (12)
GSM2079611 RNA-seq of Nortriptyline treated HSC rep 1
GSM2079612 RNA-seq of Nortriptyline treated HSC rep 2
GSM2079613 RNA-seq of Vehicle treated HSC rep 1
Relations
BioProject PRJNA314144
SRA SRP071088

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Supplementary file Size Download File type/resource
GSE78853_RAW.tar 895.5 Mb (http)(custom) TAR (of BW, TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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