Abstract
Fibrogenesis is a progressive scarring event resulting from disrupted regular wound healing due to repeated tissue injury and can end in organ failure, like in liver cirrhosis. The protagonists in this process, either liver-resident cells or patrolling leukocytes attracted to the site of tissue damage, interact with each other by soluble factors but also by direct cell–cell contact mediated by cell adhesion molecules. Since cell adhesion molecules also support binding to the extracellular matrix, they represent excellent biosensors, which allow cells to modulate their behavior based on changes in the surrounding microenvironment. In this review, we focus on selectins, cadherins, integrins and members of the immunoglobulin superfamily of adhesion molecules as well as some non-classical cell adhesion molecules in the context of hepatic fibrosis. We describe their liver-specific contributions to leukocyte recruitment, cell differentiation and survival, matrix remodeling or angiogenesis and touch on their suitability as targets in antifibrotic therapies.
Highlights
The deposition of excess fibrous connective tissue as a result of unrestrained wound healing is a highly conserved process which can afflict any chronically injured organ
16 weeks after infection was dramatically increased compared to livers of wild-type mice and correlated with a higher frequency of liver-infiltrating IL-13- and interferon γ (IFNγ)-producing lymphocytes as well as a reduction in decoy IL-13 receptor expression. These results suggest that in mice P-selectin may protect from liver fibrosis by suppressing an IFNγ response and supporting decoy IL-13 receptor synthesis [69]
Nectins and nectin-like proteins have been detected in the liver [166] and hepatic expression of some members is upregulated upon CCl4 treatment or in cirrhotic tissue [167,168], the role of these immunoglobulin superfamily of CAMs (IgCAMs) in liver inflammation and fibrosis has not yet been analyzed in detail
Summary
The deposition of excess fibrous connective tissue as a result of unrestrained wound healing is a highly conserved process which can afflict any chronically injured organ. We focus on CAMs which have been shown to be relevant to several aspects of chronic liver inflammation and fibrosis. We discuss their function in cell homing to the liver and illustrate their importance for hepatic cells in other activities such as differentiation, survival, contractility or angiogenesis. We address their suitability as clinical markers of hepatic fibrosis and briefly explore antifibrotic therapies which target CAMs in different experimental systems
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