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Retinoic acid modulates gap junctional intercellular communication in hepatocytes and hepatoma cells
C Ara1, M Massimi, L Devirgiliis Conti
1Dipartimento di Biologia di Base ed Applicata, Facoltà di Scienze, Università de L'Aquila, Via Vetoio, 67010, Coppito AQ, Italy.
Abstract:
Gap junctional communication permits the direct exchange of small molecules and ions and has been implicated in tissue homeostasis/metabolite exchange. The lack of gap junctional intercellular communication (GJIC) plays important roles in the promotion and progression of carcinogenesis. In the present study, we demonstrate that treatment of human hepatoma Hep G2 cells with retinoic acid (RA) results in increased amounts and phosphorylation of connexins, their stabilisation in plasma membrane plaques and enhanced GJIC. In cultured fetal hepatocytes, which represent a non-transformed, proliferating and incompletely differentiated liver system, the effects of RA are limited to the establishment of connexin in areas of cell-cell contact and the improvement of GJIC. This suggests that modulation of cell-cell channel communication by RA occurs differently in these two experimental models: while RA is able to revert cell transformation in Hep G2 cells, in fetal hepatocytes it may induce the expression of a more differentiated phenotype.
Insights
Retinoic acid (RA) enhances gap junctional intercellular communication (GJIC) by increasing connexins in liver cells. This suggests RA may revert cancer cell transformation and promote differentiation in liver cells.
Area of Science:
- Cell biology
- Cancer research
- Hepatology
Background:
- Gap junctional communication (GJIC) is vital for tissue homeostasis and metabolite exchange.
- Reduced GJIC is linked to cancer promotion and progression.
- Understanding GJIC modulation is crucial for cancer therapy.
Purpose of the Study:
- To investigate the effect of retinoic acid (RA) on GJIC in liver cells.
- To explore RA's role in cell transformation and differentiation.
- To elucidate the mechanisms of RA-mediated GJIC modulation.
Main Methods:
- Treatment of human hepatoma Hep G2 cells and cultured fetal hepatocytes with RA.
- Analysis of connexin expression, phosphorylation, and localization.
- Assessment of GJIC using functional assays.
Main Results:
- RA increased connexin amounts, phosphorylation, and GJIC in Hep G2 cells.
- RA enhanced connexin localization and GJIC in fetal hepatocytes.
- Differential effects of RA observed in transformed versus non-transformed liver cells.
Conclusions:
- RA modulates GJIC differently in transformed and non-transformed liver cells.
- RA may revert cancer cell transformation by enhancing GJIC.
- RA could promote a more differentiated phenotype in fetal hepatocytes.