In:
Physiological Genomics, American Physiological Society, Vol. 45, No. 7 ( 2013-04-01), p. 268-275
Abstract:
The liver consists of different cell types that together synchronize crucial roles in liver homeostasis. Since nuclear receptors constitute an important class of drug targets that are involved in a wide variety of physiological processes, we have composed the hepatic cell type-specific expression profile of nuclear receptors to uncover the pharmacological potential of liver-enriched nuclear receptors. Parenchymal liver cells (hepatocytes) and liver endothelial and Kupffer cells were isolated from virgin female C57BL/6 wild-type mice using collagenase perfusion and counterflow centrifugal elutriation. The hepatic expression pattern of 49 nuclear receptors was generated by real-time quantitative PCR using the NUclear Receptor Signaling Atlas (NURSA) program resources. Thirty-six nuclear receptors were expressed in total liver. FXR-α, EAR2, LXR-α, HNF4-α, and CAR were the most abundantly expressed nuclear receptors in liver parenchymal cells. In contrast, NUR77, COUP-TFII, LXR-α/β, FXR-α, and EAR2 were the most highly expressed nuclear receptors in endothelial and Kupffer cells. Interestingly, members of orphan receptor COUP-TF family showed a distinct expression pattern. EAR2 was highly and exclusively expressed in parenchymal cells, while COUP-TFII was moderately and exclusively expressed in endothelial and Kupffer cells. Of interest, the orphan receptor TR4 showed a similar expression pattern as the established lipid sensor PPAR-γ. In conclusion, our study provides the most complete quantitative assessment of the nuclear receptor distribution in liver reported to date. Our gene expression catalog suggests that orphan nuclear receptors such as COUP-TFII, EAR2, and TR4 may be of significant importance as novel targets for pharmaceutical interventions in liver.
Type of Medium:
Online Resource
ISSN:
1094-8341
,
1531-2267
DOI:
10.1152/physiolgenomics.00151.2012
Language:
English
Publisher:
American Physiological Society
Publication Date:
2013
detail.hit.zdb_id:
2031330-5
