Details

Autor(en) / Beteiligte

• Barbero-Becerra, Varenka J.
• Giraudi, Pablo J.
• Chávez-Tapia, Norberto C.
• Uribe, Misael
• Tiribelli, Claudio
• Rosso, Natalia

Titel

The interplay between hepatic stellate cells and hepatocytes in an in vitro model of NASH

Ist Teil von

• Toxicology in vitro, 2015-10, Vol.29 (7), p.1753-1758

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• •Global obesity epidemic dramatically increased the fatty liver disease prevalence.•In vitro models mimic liver microenvironment reproducing cellular responses to FFA.•HSC activation is fat-independent but requires hepatocytes interaction.•The gene regulation of ECM components seems to occur through paracrine mediators. A complex interplay exists between hepatocytes and hepatic stellate cells (HSC) in hepatic fibrogenesis. The activation of HSCs after liver injury leads to production of extracellular matrix (ECM). Co-culture models could be useful to mimic the liver microenvironment. This study evaluates the effect of free fatty acids (FFA) on HSC cells and the interplay with hepatocytes via both soluble-mediator and cell–cell contact. The human hepatocyte cell line (HuH7) and HSC cells (LX2) were exposed to FFA for 24h in 3 different experimental set-ups: (A) monoculture of HSC; (B) Transwell® system (effect of soluble mediators); and (C) Simultaneous Co-Culture (SCC) (cell-to-cell connections). Intracellular FFA accumulation was assessed qualitatively (microscopy) and quantitatively (flow cytometry); the activation of HSC (alpha smooth muscle actin, α-SMA) expression of ECM components were quantified by RT-PCR. FFA exposure induces intracellular fat accumulation in all the experimental set-up but the expression of α-SMA was significantly increased only in SCC. On the contrary, the expression of ECM was substantially decreased in the transwell® system. The HSC activation is independent of FFA accumulation but requires cell-to-cell interaction with hepatocyte. On the contrary, the gene regulation of ECM components seems to occur through paracrine mediators.