Deposition of cellular fibronectin increases before stellate cell activation in rat liver during ethanol feeding.
Cellular fibronectin (cFN)-a structural extracellular matrix protein-facilitates cell adhesion, migration, and differentiation during organ development; wound healing; tissue regeneration; and fibrogenic processes. cFN is deposited early in various fibrotic diseases and seems to function as a template for deposition of other extracellular matrix proteins, such as collagen type I and laminin, in the injured area. We have compared the relative changes in cFN levels with other pathogenic markers of alcoholic liver injury over time of ethanol feeding in the rat. Male Wistar rats were allowed free access to a liquid diet containing 36% of total energy as ethanol or pair-fed an isocaloric control diet for 4, 8, and 12 weeks. Serum alanine aminotransferase activity and total liver lipid were increased in ethanol-fed animals, compared with pair-fed controls after 4, 8, and 12 weeks of feeding. Liver lipid content was higher in ethanol-fed rats as early as 4 weeks and was further increased by 12 weeks of feeding. Total fibronectin and cFN protein quantity was greater in liver from ethanol-fed rats after 8 and 12 weeks (fibronectin: 2.3-fold and 2.6-fold; cFN: 4.3-fold and 2.6-fold higher than pair-fed at 8 and 12 weeks, respectively). alpha-Smooth muscle actin, an indicator of hepatic stellate cell activation, was increased in the liver of ethanol-fed rats after 12 weeks of feeding (344% higher compared with pair-fed), with no differences observed at any earlier time points. In summary, increases in hepatic immunoreactive cFN content were observed subsequent to increased liver lipid concentration, but before hepatic stellate cell activation in rats fed the ethanol-based diet. These data suggest that deposition of cFN in the liver during long-term ethanol consumption may represent an early response to injury similar to that observed in other models of liver injury and wound healing.
Gillis
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SE
Department of Human Biology and Nutritional Science, University of Guelph, Ontario, Canada.
Nagy
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LE
D000199:Actins / Q000378:metabolism; D000818:Animals; D003094:Collagen / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005235:Fatty Liver, Alcoholic / Q000473:pathology; D005353:Fibronectins / Q000378:metabolism*; D008099:Liver / Q000473:pathology; D008104:Liver Cirrhosis, Alcoholic / Q000473:pathology*; D008111:Liver Function Tests; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000199:Actins; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D003094:Collagen