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J Toxicol Sci ; 45(1): 25-35, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31932555

RESUMO

In this study, we found that nuclear receptors FXR and LXR (originally characterized as regulatory factors involved in cholesterol/bile acid homeostasis) regulate the expression of Oct3/4, a marker for cell differentiation, in both normal renal-derived cell line HK-2 and renal adenocarcinoma cell line ACHN. Down-regulation of Oct3/4 expression by activating FXR and LXR occurs only in normal renal cell-derived HK-2 cells. We also found that the RNA-binding protein, ELAVL2, oppositely regulates Oct3/4 expressions in HK-2 and ACHN cells. Moreover, we revealed that LXR-alpha and LXR-beta regulate each other's expression. Although an LXR-beta-specific agonist is assumed to be the basis for an anti-arteriosclerotic drug that only stimulates reverse cholesterol transport, our findings show that the development of such an anti-arteriosclerotic drug would require further elucidation of the complex mechanism of LXR-alpha and LXR-beta regulation.


Assuntos
Adenocarcinoma , Regulação da Expressão Gênica , Neoplasias Renais , Rim/citologia , Receptores X do Fígado/genética , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo , Receptores Citoplasmáticos e Nucleares/genética , Arteriosclerose/tratamento farmacológico , Linhagem Celular , Colesterol/metabolismo , Regulação para Baixo , Descoberta de Drogas , Proteína Semelhante a ELAV 2/genética , Humanos
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