Dataset Information

Prevention of Cell Growth by Suppression of Villin Expression in Lithocholic Acid-Stimulated HepG2 Cells.

ABSTRACT: 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.

SUBMITTER: Ozeki M

PROVIDER: S-EPMC6354318 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Prevention of Cell Growth by Suppression of Villin Expression in Lithocholic Acid-Stimulated HepG2 Cells.

Ozeki Munetaka M Aini Wulamujiang W Miyagawa-Hayashino Aya A Tamaki Keiji K

The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 20181010 2

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 cy ...[more]

PMID: 30303767

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Project description:Salusin‑β and adiponectin receptor 1 (adipoR1) serve important roles in the development of certain cardiovascular diseases and lipid metabolism. However, to the best of our knowledge, the relationship between salusin‑β and adipoR1, and their underlying mechanisms of action, currently remain unclear. In the present study, lentiviral vectors designed to overexpress salusin‑β or knock down salusin‑β expression were used in 293T and HepG2 cells. Semi‑quantitative PCR was performed to investigate the relationship between salusin‑β and adipoR1 mRNA expression in 293T cells. Western blotting was used to assess the protein expression levels of adipoR1, adenosine monophosphate‑activated protein kinase (AMPK), acetyl‑CoA carboxylase (ACC) and carnitine palmitoyl transferase 1A (CPT‑1A) in transfected HepG2 cells. Simultaneously, HepG2 cells were treated with an adipoR1 inhibitor (thapsigargin) or agonist (AdipoRon) and the resultant changes in the expression levels of the aforementioned proteins were observed. Oil Red O staining and measurements of cellular triglyceride levels were performed to assess the extent of lipid accumulation in HepG2 cells. The results demonstrated that salusin‑β overexpression downregulated adipoR1 expression and inhibited the phosphorylation of AMPK and ACC, which led to decreased CPT‑1A protein expression. By contrast, salusin‑β knockdown increased adipoR1 expression and promoted the phosphorylation of AMPK and ACC, which conversely enhanced CPT‑1A protein expression. Treatment with adipoR1 agonist, AdipoRon, reversed the effects of salusin‑β overexpression. In addition, salusin‑β overexpression enhanced intracellular lipid accumulation in HepG2 cells induced by free fatty acid treatment. These findings highlighted the potential regulatory role of salusin‑β in adipoR1‑mediated signaling pathways. To conclude, the present study provided insights into the regulation of fatty acid metabolism by the liver. In particular, salusin‑β may serve as a potential target for the therapeutic intervention of metabolic disorders of lipids.

Dataset Information

Prevention of Cell Growth by Suppression of Villin Expression in Lithocholic Acid-Stimulated HepG2 Cells.

Publications

Prevention of Cell Growth by Suppression of Villin Expression in Lithocholic Acid-Stimulated HepG2 Cells.

Similar Datasets

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