20 - World Journal of Gastroenterology

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doi:10.3748/wjg.v17.i20.2482
Natalia A Osna, MD, PhD, Series Editor
Fibronectin: Functional character and role in alcoholic liver
disease
Razia S Aziz-Seible, Carol A Casey
Razia S Aziz-Seible, Department of Biomedical Sciences,
Creighton University, 2500 California Plaza, Omaha, NE 68178,
United States
Carol A Casey, Department of Biochemistry and Molecular
Biology, University of Nebraska Medical Center, 985870 Nebraska
Medical Center, Omaha, NE 68198-5870, United States
Carol A Casey, Department of Internal Medicine, University
of Nebraska Medical Center, 986350 Nebraska Medical Center,
Omaha, NE 68198-6350, United States
Carol A Casey, The Liver Study Unit, Omaha Veterans Affairs
Medical Center, 4101 Woolworth Avenue, Omaha, NE 68105,
United States
Author contributions: Aziz-Seible RS and Casey CA both contributed
to the preparation of this manuscript.
Supported by The National Institute on Alcohol Abuse and Alcoholism
and the US Department of Veterans Affairs
Correspondence to: Carol A Casey, PhD, The Liver Study
Unit, Omaha Veterans Affairs Medical Center, 4101 Woolworth
Avenue, Omaha, NE 68105, United States. ccasey@unmc.edu
Telephone: +1-402-9953737 Fax: +1-402-4490604
Received: January 21,2011 Revised: April 7, 2011
Accepted: April 14, 2011
Published online: May 28, 2011
Abstract
Fibronectins are adhesive glycoproteins that can be
found in tissue matrices and circulating in various fluids
of the body. The variable composition of fibronectin
molecules facilitates a diversity of interactions with cell
surface receptors that suggest a role for these proteins
beyond the structural considerations of the extracellular
matrix. These interactions implicate fibronectin in
the regulation of mechanisms that also determine cell
behavior and activity. The two major forms, plasma
fibronectin (pFn) and cellular fibronectin (cFn), exist
as balanced amounts under normal physiological conditions.
However, during injury and/or disease, tissue
and circulating levels of cFn become disproportionately
elevated. The accumulating cFn, in addition to being a
consequence of prolonged tissue damage, may in fact
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2482
World J Gastroenterol 2011 May 28; 17(20): 2482-2499
ISSN 1007-9327 (print) ISSN 2219-2840 (online)
© 2011 Baishideng. All rights reserved.
stimulate cellular events that promote further damage.
In this review, we summarize what is known regarding
such interactions between fibronectin and cells that may
influence the biological response to injury. We elaborate
on the effects of cFn in the liver, specifically under a
condition of chronic alcohol-induced injury. Studies have
revealed that chronic alcohol consumption stimulates
excess production of cFn by sinusoidal endothelial cells
and hepatic stellate cells while impairing its clearance by
other cell types resulting in the build up of this glycoprotein
throughout the liver and its consequent increased
availability to influence cellular activity that could promote
the development of alcoholic liver disease. We
describe recent findings by our laboratory that support a
plausible role for cFn in the promotion of liver injury under
a condition of chronic alcohol abuse and the implications
of cFn stimulation on the pathogenesis of alcoholic
liver disease. These findings suggest an effect of cFn in
regulating cell behavior in the alcohol-injured liver that
is worth further characterizing not only to gain a more
comprehensive understanding of the role this reactive
glycoprotein plays in the progression of injury but also
for the insight further studies could provide towards
the development of novel therapies for alcoholic liver
disease.
© 2011 Baishideng. All rights reserved.
TOPIC HIGHLIGHT
Key words: Fibronectin; Liver disease; Alcoholic liver
disease; Endocytosis; Cellular fibronectin
Peer reviewer: Fernando J Corrales, Associate Professor of
Biochemistry, Division of Hepatology and Gene Therapy, Proteomics
Laboratory, CIMA, University of Navarra, Avd. Pío
XII, 55, Pamplona, 31008, Spain
Aziz-Seible RS, Casey CA. Fibronectin: Functional character
and role in alcoholic liver disease. World J Gastroenterol 2011;
17(20): 2482-2499 Available from: URL: http://www.wjgnet.
com/1007-9327/full/v17/i20/2482.htm DOI: http://dx.doi.
org/10.3748/wjg.v17.i20.2482
May 28, 2011|Volume 17|Issue 20|