The present review provides the state of the art of the current knowledge concerning gap junctional channels and their roles in liver functioning. In the first part, we summarize some relevant biochemical properties of hepatic gap junctional channels, including their structure and regulation. In the second part, we discuss the involvement of gap junctional channels in the occurrence of liver cell growth, liver cell differentiation, and liver cell death. We further exemplify their relevance in hepatic pathophysiology. Finally, a number of directions for future liver gap junctional channel research are proposed, and the up-regulation of gap junctional channel activity as a novel strategy in (liver) cancer therapy is illustrated.

In liver, like in other multicellular systems, the establishment of cellular contacts is a prerequisite for normal functioning. In particular, well-defined cell junctions between hepatocytes, including adherens junctions, desmosomes, tight junctions, and gap junctions, are known to play key roles in the performance of liver-specific functionality. In a first part of this review article, we summarize the current knowledge concerning cell junctions and their roles in hepatic (patho)physiology. In a second part, we discuss their relevance in liver-based in vitro modeling, thereby highlighting the use of primary hepatocyte cultures as suitable in vitro models for preclinical pharmaco-toxicological testing. We further describe the actual strategies to regain and maintain cell junctions in these in vitro systems over the long-term.

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Controlling both growth and differentiation of stem cells and their differentiated somatic progeny is a challenge in numerous fields, from preclinical drug development to clinical therapy. Recently, new insights into the underlying molecular mechanisms have unveiled key regulatory roles of epigenetic marks driving cellular pluripotency, differentiation and self-renewal/proliferation. Indeed, the transcription of genes, governing cell-fate decisions during development and maintenance of a cell's differentiated status in adult life, critically depends on the chromatin accessibility of transcription factors to genomic regulatory and coding regions. In this review, we discuss the epigenetic control of (liver-specific) gene-transcription and the intricate interplay between chromatin modulation, including histone (de)acetylation and DNA (de)methylation, and liver-enriched transcription factors. Special attention is paid to their role in directing hepatic differentiation of primary hepatocytes and stem cells in vitro.

The controlled pre-damaged forearm method with tape stripping appears to be a suitable model to study the effects of repetitive wiping on irritated skin with disposable handkerchiefs of different quality. More specifically, the model seems applicable to mimic the nasolabial skin damage observed during a common cold associated with frequent use of disposable handkerchiefs.