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Adhesion to the extracellular matrix is positively regulated by retinoic acid in HepG2 cells
Author(s) -
Massimi Mara,
Devirgiliis Laura Conti
Publication year - 2007
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2006.01391.x
Subject(s) - focal adhesion , paxillin , extracellular matrix , microbiology and biotechnology , integrin , ptk2 , retinoic acid , cell adhesion , cytoskeleton , cell adhesion molecule , internalization , biology , adhesion , chemistry , signal transduction , phosphorylation , cell culture , cell , biochemistry , protein kinase a , mitogen activated protein kinase kinase , genetics , organic chemistry
Aims: In this work, we aimed to investigate the possible modulation of cell–matrix interactions by retinoic acid (RA), in view of the well‐known role of the extracellular matrix (ECM) and integrins in hepatocyte differentiation and proliferation. For this purpose, we analysed the adhesion ability of HepG2 cells on different substrates in the presence and absence of RA evaluating both the expression and cellular localisation of major proteins involved in focal contacts, using Western blot and confocal microscopy. Results: A positive and substrate‐dependent effect of RA on cell–matrix adhesion was observed after long‐term culture. The increased adhesiveness in the treated cells was accompanied by an enhanced expression of β1 and α3 integrin subunits, together with a redistribution of β1 receptors clustered at the basal surface. In contrast, the levels of focal adhesion kinase (FAK), paxillin and α‐actinin were unchanged, as was the phosphorylation state of FAK. Nonetheless, a stronger association between β1 integrin and intracytoplasmatic proteins of focal contacts was observed in coimmunoprecipitation experiments after RA treatment, suggesting improved connection with the actin cytoskeleton. These results are consistent with previously described antiproliferative and differentiative effects of RA on transformed hepatocytes, and confirm the hypothesis of a direct influence of RA on specific adhesion molecules.