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Toxicol In Vitro. 2015 Oct;29(7):1753-8. doi: 10.1016/j.tiv.2015.07.010. Epub 2015 Jul 14.

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

Author information

1
Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Puente de Piedra 150, Col. Toriello Guerra, Tlalpan, C.P. 14050 Mexico City, Mexico; Centro Studi Fegato (CSF) - Liver Research Center, Fondazione Italiana Fegato, Bldg Q AREA Science Park, Basovizza Campus SS 14 km 163.5, 34149 Trieste, Italy. Electronic address: varenka_bb@hotmail.com.
2
Centro Studi Fegato (CSF) - Liver Research Center, Fondazione Italiana Fegato, Bldg Q AREA Science Park, Basovizza Campus SS 14 km 163.5, 34149 Trieste, Italy. Electronic address: pablo.giraudi@csf.units.it.
3
Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Puente de Piedra 150, Col. Toriello Guerra, Tlalpan, C.P. 14050 Mexico City, Mexico. Electronic address: khavez@gmail.com.
4
Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Puente de Piedra 150, Col. Toriello Guerra, Tlalpan, C.P. 14050 Mexico City, Mexico. Electronic address: muribe@medicasur.org.mx.
5
Centro Studi Fegato (CSF) - Liver Research Center, Fondazione Italiana Fegato, Bldg Q AREA Science Park, Basovizza Campus SS 14 km 163.5, 34149 Trieste, Italy; Department of Medical Sciences, University of Trieste, 34100 Trieste, Italy. Electronic address: ctliver@csf.units.it.
6
Centro Studi Fegato (CSF) - Liver Research Center, Fondazione Italiana Fegato, Bldg Q AREA Science Park, Basovizza Campus SS 14 km 163.5, 34149 Trieste, Italy. Electronic address: natalia.rosso@csf.units.it.

Abstract

BACKGROUND & AIM:

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.

METHODS:

The human hepatocyte cell line (HuH7) and HSC cells (LX2) were exposed to FFA for 24 h 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.

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

Extracellular matrix; Fatty acids; Hepatic stellate cells; NAFLD

PMID:
26187275
DOI:
10.1016/j.tiv.2015.07.010
[Indexed for MEDLINE]

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