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Prevention of Cell Growth by Suppression of Villin Expression in Lithocholic Acid-Stimulated HepG2 Cells.
- Source :
- Journal of Histochemistry & Cytochemistry; Feb2019, Vol. 67 Issue 2, p129-141, 13p
- Publication Year :
- 2019
-
Abstract
- Summary: 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- CELL growth
GENE expression
LITHOCHOLIC acid
LIVER injuries
MICROFILAMENT proteins
Subjects
Details
- Language :
- English
- ISSN :
- 00221554
- Volume :
- 67
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Journal of Histochemistry & Cytochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 139960116
- Full Text :
- https://doi.org/10.1369/0022155418804507