Aziz-Seible RS, McVicker BL, Kharbanda KK, Casey CA. Cellular fibronectin stimulates hepatocytes to produce factors that promote alcohol-induced liver injury. World J Hepatol 2011; 3(2): 45-55 [PMID: 21423914 DOI: 10.4254/wjh.v3.i2.45]
Corresponding Author of This Article
Carol A Casey, PhD, Professor, UNMC Department of Internal Medicine, The Liver Study Unit-Research Service (151), Department of Veterans Affairs Medical Center, 4101 Woolworth Avenue, Omaha, NE 68105, United States. ccasey@unmc.edu
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Origenal Article
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World J Hepatol. Feb 27, 2011; 3(2): 45-55 Published online Feb 27, 2011. doi: 10.4254/wjh.v3.i2.45
Cellular fibronectin stimulates hepatocytes to produce factors that promote alcohol-induced liver injury
Razia S Aziz-Seible, Benita L McVicker, Kusum K Kharbanda, Carol A Casey
Razia S Aziz-Seible, Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, 985870 Nebraska Medical Center, Omaha, NE 68198-5870, United States
Benita L McVicker, Kusum K Kharbanda, Carol A Casey, Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, 985870 Nebraska Medical Center, Omaha, NE 68198-5870, United States
Benita L McVicker, Kusum K Kharbanda, Carol A Casey, Department of Internal Medicine, University of Nebraska Medical Center, 986350 Nebraska Medical Center, Omaha, NE 68198-6350, United States
Benita L McVicker, Kusum K Kharbanda, Carol A Casey, Liver Study Unit, Omaha Veterans Affairs Medical Center, 4101 Woolworth Avenue, Omaha, NE 68105, United States
Author contributions: Aziz-Seible RS performed the experiments, analyzed the data and prepared the manuscript; McVicker BL and Kharbanda KK contributed to the preparation of this manuscript; and Casey CA contributed to the analysis of the data and the preparation of the manuscript.
Supported by the National Institute on Alcohol Abuse and Alcoholism and the US Department of Veterans Affairs
Correspondence to: Carol A Casey, PhD, Professor, UNMC Department of Internal Medicine, The Liver Study Unit-Research Service (151), Department of Veterans Affairs Medical Center, 4101 Woolworth Avenue, Omaha, NE 68105, United States. ccasey@unmc.edu
Telephone: +1-402-9953737 Fax: +1-402-4490604
Received: October 14, 2010 Revised: December 29, 2010 Accepted: November 6, 2010 Published online: February 27, 2011
Abstract
AIM: To examine the consequences of cellular fibronectin (cFn) accumulation during alcohol-induced injury, and investigate whether increased cFn could have an effect on hepatocytes (HCs) by producing factors that could contribute to alcohol-induced liver injury.
METHODS: HCs were isolated from rats fed a control or ethanol liquid diet for four to six weeks. Exogenous cFn (up to 7.5 μg/mL) was added to cells cultured for 20 h, and viability (lactate dehydrogenase,LDH), apoptosis (caspase activity) and secretion of proinflammatory cytokines (tumor necrosis factor alpha, TNF-α and interleukin 6 IL-6), matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of metalloproteinases, TIMPs) was determined. Degradation of iodinated cFn was determined over a 3 h time period in the preparations.
RESULTS: cFn degradation is impaired in HCs isolated from ethanol-fed animals, leading to its accumulation in the matrix. Addition of exogenous cFn did not affect viability of HCs from control or ethanol-fed animals, and apoptosis was affected only at the higher concentration. Secretion of MMPs, TIMPs, TNF-α and IL-6, however, was increased by exogenously added cFn, with HCs from ethanol-fed animals showing increased susceptibility compared to the controls.
CONCLUSION: These results suggest that the elevated amounts of cFn observed in alcoholic liver injury can stimulate hepatocytes to produce factors which promote further tissue damage.
