Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression data from human hepatic stellate cell line LX2 treated with suberoylanilide hydroxamic acid (SAHA) or valproic acid (VPA)

ABSTRACT: Suberoylanilide hydroxamic acid (SAHA) and valproic acid (VPA) are both histone deacetylases inhibitor (HDACi), and are able to attenuate the activation of hepatic stelllate cells. To explore the underlying molecular mechanisms, we performed gene expression profile analyses of human hepatic stellate cell line LX2 treated with SAHA or VPA for 24 hours. Duplicate experiments were performed: Untreated LX2, SAHA treated LX2 and VPA treated LX2.

INSTRUMENT(S): GeneChip Hybridization Oven 645, GeneChip Scanner 3000 7G

ORGANISM(S): Homo sapiens

SUBMITTER: Juling Ji

PROVIDER: E-MTAB-3764 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Suberoylanilide hydroxamic acid suppresses hepatic stellate cells activation by HMGB1 dependent reduction of NF-κB1.

Wang Wenwen W Yan Min M Ji Qiuhong Q Lu Jinbiao J Ji Yuhua Y Ji Juling J

PeerJ 20151103

Hepatic stellate cells (HSCs) activation is essential to the pathogenesis of liver fibrosis. Exploring drugs targeting HSC activation is a promising anti-fibrotic strategy. In the present study, we found suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, prominently suppressed the activation phenotype of a human hepatic stellate cell line-LX2. The production of collagen type I and α-smooth muscle actin (α-SMA) as well as the proliferation and migration of LX2 cells were sig ...[more]

PMID: 26557438

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Project description:Design: Persistent latently infected CD4+ T cells represent a major obstacle to HIV eradication. Histone deacetylase inhibitors (HDACis) are a promising activation therapy in a “shock and kill” strategy. However, off-target effects of HDACis on host gene expression are poorly understood in primary cells of the immune system. We hypothesized that HDACi-modulated genes would be best identified with a dose response analysis. Methods: Resting primary CD4+ T cells were treated with increasing concentrations (0.34, 1, 3, or 10 μM) of the HDACi, suberoylanilide hydroxamic acid (SAHA), for 24 hours and then subjected to microarray gene expression analysis. Genes with dose-correlated expression were identified with a likelihood ratio test using Isogene GX and a subset of these genes with a consistent trend of up or downregulation at each dose of SAHA were identified as dose-responsive. Histone modifications were characterized in promoter regions of the top 6 SAHA dose-responsive genes by RT-qPCR analysis of immunopreciptated chromatin (ChIP). Results: A large number of genes were shown to be up (N=657) or down (N=725) regulated by SAHA in a dose-responsive manner (FDR p-value < 0.05 and fold change ≥ |2|). Several of these genes (CTNNAL1, DPEP2, H1F0, IRGM, PHF15, and SELL) are potential in vivo biomarkers of SAHA activity. SAHA dose-responsive gene categories included transcription factors, HIV restriction factors, histone methyltransferases, and host proteins that interact with HIV proteins or the HIV LTR. Pathway analysis suggested net downregulation of T cell activation with increasing SAHA dose. Histone acetylation was not correlated with host expression, but plausible alternative mechanisms for SAHA-modulated expression were identified. Conclusions: Numerous host genes in CD4+ T cells are modulated by SAHA in a dose-responsive manner, including genes that may negatively influence HIV activation from latency. Our study suggests that SAHA influences gene expression through a confluence of several mechanisms, including histone acetylation, histone methylation, and altered expression and activity of transcription factors.

Dataset Information

Expression data from human hepatic stellate cell line LX2 treated with suberoylanilide hydroxamic acid (SAHA) or valproic acid (VPA)

Publications

Suberoylanilide hydroxamic acid suppresses hepatic stellate cells activation by HMGB1 dependent reduction of NF-κB1.

Similar Datasets

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