Superfund Research Program
Detection and Models of Toxicant Exposure
Center Director: Robert H. Tukey
Grant Number: P42ES010337
Funding Period: 2000-2023
Program Links
Title: A master cistromic circuit governing hepatic fibrogenesis [expression array]
Accession Number: E-GEOD-41579
Link to Dataset: http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-41579/
Repository: ArrayExpress
Data Type(s): Gene Expression
Experiment Type(s): Transcription profiling by array
Organism(s): Rattus norvegicus
Summary: Liver fibrosis is a reversible wound-healing response to liver injury and hepatic stellate cells (HSCs) are central cellular players that mediate hepatic fibrogenesis. However, the molecular mechanisms that govern this process remain unclear. Expression profiling was used to explore the potential impact of VDR signaling in TGF 1 and TGF 1+1,25(OH)2D3-treated primary rat HSCs. Notably, 1,25(OH)2D3 treatment attenuated the culture-induced activation of HSCs, such that the transcriptome of treated cells closely resembled that of freshly isolated quiescent cells (Figure 2A), and co-treatment of 1,25(OH)2D3 together with TGF resulted in considerable repression of a large set of TGF induced genes. We also demonstrated that in primary mouse HSCs, calcipotriol potently repressed fibrotic gene expression, suggesting that the anti-TGF properties of VDR agonists are likely conserved across mammalian species. Total RNA from primary rat HSCs were isolated and treated 1,25(OH)2D3 (100nM) for 24 hours to determine how Vitamin D ligands can impact the activated stellate cell state.
Publication(s) associated with this dataset:- Ding N, Yu RT, Subramaniam N, Sherman MH, Wilson C, Rao R, Leblanc M, Coulter S, He M, Scott C, Lau SL, Atkins AR, Barish GD, Gunton JE, Liddle C, Downes M, Evans RM. 2013. A vitamin D receptor / SMAD genomic circuit gates hepatic fibrotic response. Cell 153(3):601-613. doi:10.1016/j.cell.2013.03.028 PMID:23622244 PMCID:PMC3673534