Identification of stanniocalcin 2 as a novel aryl hydrocarbon receptor target genes

Tod A. Harper, Aditya D. Joshi, Cornelis Elferink

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Proper hepatocyte function is vital for survival;thus, unrepaired destruction of the parenchymal tissue leading to liver decompensation is devastating. Therefore, understanding the homeostatic process regulating liver regeneration is clinically important, and evidence that the aryl hydrocarbon receptor (AhR) can promote cell survival after intrinsic apoptotic stimuli is integral to the regenerative process. The current study uses primary hepatocytes to identify survival mechanisms consistent with normal AhR biology. Taking advantage of the Cre-lox system to manipulate AhR status, we designed a comprehensive microarray analysis to identify immediate and direct changes in the transcriptome concomitant with the loss of the AhR. As a result, we identified a unique data set with minimal overlap, compared with previous array studies, culminating in the identification of Stanniocalcin 2 (Stc2) as a novel receptor target gene previously reported to have a cytoprotective role in endoplasmic reticulum stress. The Stc2 promoter contains multiple putative xenobiotic response elements clustered in a 250-bp region that was shown to recruit the AhR by chromatin immunoprecipitation. Of interest, Stc2 gene expression is refractory to classic exogenous AhR agonists, but responds to cellular stress in an AhR-dependent mechanism consistent with a process promoting cell survival.

Original languageEnglish (US)
Pages (from-to)579-588
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Volume344
Issue number3
DOIs
StatePublished - Mar 2013

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Aryl Hydrocarbon Receptors
Genes
Hepatocytes
Cell Survival
Liver Regeneration
Endoplasmic Reticulum Stress
Chromatin Immunoprecipitation
Response Elements
Xenobiotics
Microarray Analysis
teleocalcin
Transcriptome
Gene Expression
Liver

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

Identification of stanniocalcin 2 as a novel aryl hydrocarbon receptor target genes. / Harper, Tod A.; Joshi, Aditya D.; Elferink, Cornelis.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 344, No. 3, 03.2013, p. 579-588.

Research output: Contribution to journalArticle

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