Dataset Information

Transcriptomic signatures of peroxisome proliferator-activated receptor ? (PPAR?) in different mouse liver models identify novel aspects of its biology.

ABSTRACT:

Background

The peroxisome proliferator-activated receptor alpha (PPAR?) is a ligand-activated transcription factor that regulates lipid catabolism and inflammation and is hepatocarcinogenic in rodents. It is presumed that the functions of PPAR? in liver depend on cross-talk between parenchymal (hepatocytes) and non-parenchymal (Kupffer and endothelial cells) fractions as well as inter-organ interactions. In order to determine how cellular composition and inter-organ interactions influence gene expression upon pharmacological activation of PPAR?, we performed a meta-analysis of transcriptomics data obtained from mouse hepatocytes (containing only the parenchymal fraction), mouse liver slices (containing both fractions), and mouse livers exposed to a PPAR? agonist. The aim was to obtain a comprehensive view of common and model-specific PPAR?-dependent genes and biological processes to understand the impact of cross-talk between parenchymal and non-parenchymal fractions as well as the effect of inter-organ interactions on the hepatic PPAR? transcriptome.To this end we analyzed microarray data of experiments performed in mouse primary hepatocytes treated with the PPAR? agonist Wy14643 for 6 or 24 h (in vitro), mouse precision cut liver slices treated with Wy14643 for 24 h (ex vivo), and livers of wild type and Ppara knockout mice treated with Wy14643 for 6 h or 5 days (in vivo).

Results

In all models, activation of PPAR? significantly altered processes related to various aspects of lipid metabolism. In ex vivo and in vivo models, PPAR? activation significantly regulated processes involved in inflammation; these processes were unaffected in hepatocytes. Only in vivo models showed significant regulation of genes involved in coagulation, carcinogenesis, as well as vesicular trafficking and extracellular matrix.

Conclusions

PPAR?-dependent regulation of genes/processes involved in lipid metabolism is mostly independent of the presence of non-parenchymal cells or systemic factors, as it was observed in all liver models. PPAR?-dependent regulation of inflammatory genes requires the presence of non-parenchymal cells, as it was observed only ex vivo and in vivo. However, the full spectrum of PPAR? biology at the level of lipid metabolism, immunity, carcinogenesis, as well as novel aspects of PPAR? signaling such as coagulation, vesicular trafficking and the extracellular matrix, seems to require systemic factors, as it was observed exclusively in vivo.

SUBMITTER: Szalowska E

PROVIDER: S-EPMC4378209 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Publications

Transcriptomic signatures of peroxisome proliferator-activated receptor α (PPARα) in different mouse liver models identify novel aspects of its biology.

Szalowska Ewa E Tesfay Haftu A HA van Hijum Sacha A F T SA Kersten Sander S

BMC genomics 20141215

<h4>Background</h4>The peroxisome proliferator-activated receptor alpha (PPARα) is a ligand-activated transcription factor that regulates lipid catabolism and inflammation and is hepatocarcinogenic in rodents. It is presumed that the functions of PPARα in liver depend on cross-talk between parenchymal (hepatocytes) and non-parenchymal (Kupffer and endothelial cells) fractions as well as inter-organ interactions. In order to determine how cellular composition and inter-organ interactions influenc ...[more]

PMID: 25511156

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