Open AccessEndothelial cell‐derived matrix promotes the metabolic functional maturation of hepatocyte via integrin‐Src signalling
Author(s) -
Guo Xinyue,
Li Weihong,
Ma Minghui,
Lu Xin,
Zhang Haiyan
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13195
Subject(s) - microbiology and biotechnology , extracellular matrix , hepatocyte nuclear factor 4 , integrin , fibronectin , hepatocyte , phosphorylation , chemistry , pregnane x receptor , hepatocyte growth factor , biology , transcription factor , nuclear receptor , cell , receptor , biochemistry , in vitro , gene
The extracellular matrix ( ECM ) microenvironment is involved in the regulation of hepatocyte phenotype and function. Recently, the cell‐derived extracellular matrix has been proposed to represent the bioactive and biocompatible materials of the native ECM . Here, we show that the endothelial cell‐derived matrix ( EC matrix) promotes the metabolic maturation of human adipose stem cell‐derived hepatocyte‐like cells ( hASC ‐ HLC s) through the activation of the transcription factor forkhead box protein A2 ( FOXA 2) and the nuclear receptors hepatocyte nuclear factor 4 alpha ( HNF 4α) and pregnane X receptor ( PXR ). Reducing the fibronectin content in the EC matrix or silencing the expression of α5 integrin in the hASC ‐ HLC s inhibited the effect of the EC matrix on Src phosphorylation and hepatocyte maturation. The inhibition of Src phosphorylation using the inhibitor PP 2 or silencing the expression of Src in hASC ‐ HLC s also attenuated the up‐regulation of the metabolic function of hASC ‐ HLC s in a nuclear receptor‐dependent manner. These data elucidate integrin‐Src signalling linking the extrinsic EC matrix signals and metabolic functional maturation of hepatocyte. This study provides a model for studying the interaction between hepatocytes and non‐parenchymal cell‐derived matrix.