Fibronectin: Functional character and role in alcoholic liver disease

Abstract

Fibronectins are adhesive glycoproteins that can befound in tissue matrices and circulating in various fluidsof the body. The variable composition of fibronectinmolecules facilitates a diversity of interactions with cellsurface receptors that suggest a role for these proteinsbeyond the structural considerations of the extracellularmatrix. These interactions implicate fibronectin inthe regulation of mechanisms that also determine cellbehavior and activity. The two major forms, plasmafibronectin (pFn) and cellular fibronectin (cFn), existas balanced amounts under normal physiological conditions.However, during injury and/or disease, tissueand circulating levels of cFn become disproportionatelyelevated. The accumulating cFn, in addition to being aconsequence of prolonged tissue damage, may in factstimulate cellular events that promote further damage.In this review, we summarize what is known regardingsuch interactions between fibronectin and cells that mayinfluence the biological response to injury. We elaborateon the effects of cFn in the liver, specifically under acondition of chronic alcohol-induced injury. Studies haverevealed that chronic alcohol consumption stimulatesexcess production of cFn by sinusoidal endothelial cellsand hepatic stellate cells while impairing its clearance byother cell types resulting in the build up of this glycoproteinthroughout the liver and its consequent increasedavailability to influence cellular activity that could promotethe development of alcoholic liver disease. Wedescribe recent findings by our laboratory that support aplausible role for cFn in the promotion of liver injury undera condition of chronic alcohol abuse and the implicationsof cFn stimulation on the pathogenesis of alcoholicliver disease. These findings suggest an effect of cFn inregulating cell behavior in the alcohol-injured liver thatis worth further characterizing not only to gain a morecomprehensive understanding of the role this reactiveglycoprotein plays in the progression of injury but alsofor the insight further studies could provide towardsthe development of novel therapies for alcoholic liverdisease. © 2011 Baishideng.