2011
The interplay of the aryl hydrocarbon receptor and beta-catenin alters both AhR-dependent transcription and Wnt/beta catenin signaling in liver progenitors.
PROCHÁZKOVÁ, Jiřina; Markéta KABÁTKOVÁ; Vítězslav BRYJA; Lenka UMANNOVÁ; Ondřej BERNATÍK et al.Základní údaje
Originální název
The interplay of the aryl hydrocarbon receptor and beta-catenin alters both AhR-dependent transcription and Wnt/beta catenin signaling in liver progenitors.
Autoři
PROCHÁZKOVÁ, Jiřina; Markéta KABÁTKOVÁ; Vítězslav BRYJA; Lenka UMANNOVÁ ORCID; Ondřej BERNATÍK; Alois KOZUBÍK; Miroslav MACHALA a Jan VONDRÁČEK
Vydání
Toxicological sciences, 2011, 1096-6080
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
30105 Physiology
Stát vydavatele
Velká Británie a Severní Irsko
Utajení
není předmětem státního či obchodního tajemství
Odkazy
Impakt faktor
Impact factor: 4.652
Označené pro přenos do RIV
Ano
Kód RIV
RIV/00216224:14310/11:00050224
Organizační jednotka
Přírodovědecká fakulta
UT WoS
Klíčová slova anglicky
Wnt signaling; dioxin; intercellular junctions; contact inhibition; liver progenitor cells; differentiation
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 17. 6. 2014 13:15, Mgr. Markéta Kabátková, Ph.D.
Anotace
V originále
beta-catenin is a key integrator of cadherin-mediated cell-cell adhesion and transcriptional regulation through the Wnt/beta-catenin pathway, which plays an important role in liver biology. Using a model of contact-inhibited liver progenitor cells, we examined the interactions of Wnt/beta-catenin signaling with the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, which mediates the toxicity of dioxin-like compounds, including their effects on development and hepatocarcinogenesis. We found that AhR and Wnt/beta-catenin cooperated in the induction of AhR transcriptional targets, such as Cyp1a1 and Cyp1b1. However, simultaneously, the activation of AhR led to a decrease of dephosphorylated active beta-catenin pool, as well as to hypophosphorylation of Dishevelled, participating in regulation of Wnt signaling. A sustained AhR activation by its model ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), led to a downregulation of a number of Wnt/beta-catenin pathway target genes. TCDD also induced a switch in cytokeratin expression, where downregulation of cytokeratins 14 and 19 was accompanied with an increased cytokeratin 8 expression. Together with a downregulation of additional markers associated with stem-like phenotype, this indicated that the AhR activation interfered with differentiation of liver progenitors.
Návaznosti
| GD204/09/H058, projekt VaV |
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| MSM0021622430, záměr |
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