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首页> 外文期刊>Biochimica et biophysica acta. Molecular basis of disease: BBA >Expression patterns of nuclear receptors in parenchymal and non parenchymal mouse liver cells and their modulation in cholestasis
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Expression patterns of nuclear receptors in parenchymal and non parenchymal mouse liver cells and their modulation in cholestasis

机译：实质和非实质小鼠肝细胞中核受体的表达模式及其在胆汁淤积中的调节

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摘要

Nuclear receptors (NR), the largest family of transcription factors, control many physiological and pathological processes. To gain insight into hepatic NR and their potential as therapeutic targets in cholestatis, we determined their expression in individual cell types of the mouse liver in normal and cholestatic conditions. Hepatocytes, cholangiocytes, hepatic stellate cells (HSC), sinusoidal endothelial cells (SEC) and Kupffer cells (KC) were isolated from the liver of mice with acute or chronic cholestasis (ie. bile duct-ligated or Abcb4(-/-) mice, respectively) and healthy controls. The expression of 43 out of the 49 NR was evidenced by RT-qPCR in one or several liver cell types. Expression of four NR was restricted to non-parenchymal liver cells. In normal conditions, NR were expressed at higher levels in individual cell types when compared to total liver. Half of the NR expressed in the liver had maximal expression in non-parenchymal cells. After bile duct ligation, NR mRNA changes occurred mostly in non-parenchymal cells and mainly consisted in down-regulations. In Abcb4(-/-) mice, NR mRNA changes were equally frequent in hepatocytes and non-parenchymal cells. Essentially down regulations were found in hepatocytes, HSC and cholangiocytes, as opposed to up-regulations in SEC and KC. While undetectable in total liver, Vdr expression was up-regulated in all non-parenchymal cells in Abcb4(-/-) mice. In conclusion, non-parenchymal liver cells are a major site of NR expression. During cholestasis, NR expression is markedly altered mainly by down-regulations, suggesting major changes in metabolic activity. Thus, non-parenchymal cells are important new targets to consider in NR-directed therapies.
机译：核受体（NR），最大的转录因子家族，控制许多生理和病理过程。为了深入了解肝脏NR及其作为胆汁素中治疗靶标的潜力，我们在正常和胆汁淤积条件下确定了在小鼠肝脏的个体细胞类型中的表达。肝细胞，肝星状细胞（HSC），正弦内皮细胞（SEC）和Kupffer细胞（KC）与急性或慢性胆汁淤积（即胆管连接或ABCB4（ - / - ）小鼠的小鼠分离出来分别为健康控制。通过RT-QPCR在一种或几种肝细胞类型中证明了49个NR中的43的表达。四个NR的表达仅限于非实质肝细胞。在正常条件下，与总肝脏相比，NR在单个细胞类型中以更高的水平表达。肝脏中表达的一半具有在非实质细胞中的最大表达。在胆管结扎后，NR mRNA变化主要发生在非实质细胞中，主要是在下行规定中组成。在ABCB4（ - / - ）小鼠中，NR mRNA的变化在肝细胞和非实质细胞中同样频繁频繁。基本上在肝细胞，HSC和胆管细胞中发现了规则，而不是在SEC和KC的上规规定。虽然在总肝脏中不可检测到的虽然在ABCB4（ - / - ）小鼠中的所有非实质细胞中，VDR表达上调。总之，非实质肝细胞是NR表达的主要部位。在胆汁淤积期间，NR表达主要是由下行规定的显着改变，表明代谢活动的重大变化。因此，非实质细胞是在NR定向疗法中考虑的重要新目标。

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