胆酸刺激 HepG2 细胞中抑制微丝束蛋白表达抑制细胞生长。
Prevention of Cell Growth by Suppression of Villin Expression in Lithocholic Acid-Stimulated HepG2 Cells.
机构信息
Department of Forensic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
出版信息
J Histochem Cytochem. 2019 Feb;67(2):129-141. doi: 10.1369/0022155418804507. Epub 2018 Oct 10.
Cholestasis is a condition wherein bile flow is interrupted and lithocholic acid is known to play a key role in causing severe liver injury. In this study, we performed in-depth analysis of the morphological changes in bile canaliculi and the biological role of villin in cholestasis using lithocholic acid-stimulated HepG2 human hepatocarcinoma cells. We confirmed disruption of the bile canaliculi in liver sections from a liver allograft patient with cholestasis. Lithocholic acid caused strong cytotoxicity in HepG2 cells, which was associated with abnormal morphology. Lithocholic acid reduced villin expression, which recovered in the presence of nuclear receptor agonists. Furthermore, villin mRNA expression increased following small interfering RNA (siRNA)-mediated knockdown of the nuclear farnesoid X receptor and pregnane X receptor. Villin knockdown using siRNA caused cell growth arrest in HepG2 cells. The effect of villin-knockdown on whole-genome expression in HepG2 cells was analyzed by DNA microarray. Our data suggest that lithocholic acid caused cell growth arrest by suppressing villin expression via farnesoid X receptor and pregnane X receptor in HepG2 cells.
胆汁淤积是一种胆汁流动受阻的疾病，已知胆酸在引起严重肝损伤方面起着关键作用。在这项研究中，我们使用胆酸刺激的 HepG2 人肝癌细胞对胆小管的形态变化和微丝蛋白的生物学作用进行了深入分析。我们确认了胆汁淤积症肝移植患者肝组织切片中小胆管的破坏。胆酸对 HepG2 细胞具有强烈的细胞毒性，与异常形态有关。胆酸降低了微丝蛋白的表达，而核受体激动剂的存在使其恢复。此外，小干扰 RNA（siRNA）介导的核法尼醇 X 受体和孕烷 X 受体敲低后，微丝蛋白 mRNA 表达增加。使用 siRNA 敲低微丝蛋白会导致 HepG2 细胞生长停滞。通过 DNA 微阵列分析了微丝蛋白敲低对 HepG2 细胞全基因组表达的影响。我们的数据表明，胆酸通过法尼醇 X 受体和孕烷 X 受体抑制 HepG2 细胞中微丝蛋白的表达，导致细胞生长停滞。
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