In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-09-05)
Abstract:
The aryl hydrocarbon receptor (AhR) has roles in cell proliferation, differentiation and organ homeostasis, including the liver. AhR depletion induces undifferentiation and pluripotency in normal and transformed cells. Here, AhR-null mice ( AhR −/−) were used to explore whether AhR controls liver regeneration and carcinogenesis by restricting the expansion of stem-like cells and the expression of pluripotency genes. Short-term CCl 4 liver damage was earlier and more efficiently repaired in AhR −/− than in AhR +/+ mice. Stem-like CK14 + and TBX3 + and pluripotency-expressing OCT4 + and NANOG + cells expanded sooner in AhR −/− than in AhR +/+ regenerating livers. Stem-like side population cells (SP) isolated from AhR −/− livers had increased β-catenin (β-Cat) signaling with overexpression of Axin2 , Dkk1 and Cyclin D1 . Interestingly, β-Cat , Axin2 and Dkk1 also increased during regeneration but more notably in AhR-null livers. Liver carcinogenesis induced by diethylnitrosamine (DEN) produced large carcinomas in all AhR −/− mice but mostly premalignant adenomas in less than half of AhR +/+ mice. AhR-null tumoral tissue, but not their surrounding non-tumoral parenchyma, had nuclear β-Cat and Axin2 overexpression. OCT4 and NANOG were nevertheless similarly expressed in AhR +/+ and AhR −/− lesions. We suggest that AhR may serve to adjust liver repair and to block tumorigenesis by modulating stem-like cells and β-Cat signaling.
Type of Medium:
Online Resource
ISSN:
2045-2322
DOI:
10.1038/s41598-017-10984-w
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2017
detail.hit.zdb_id:
2615211-3
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