FIBRONECTIN MESSENGER-RNA (FN-V95(+)) IS INCREASED IN THE LIVER OF OLD SPRAGUE-DAWLEY RATS - EFFECT OF FOOD RESTRICTION

Because fibronectin (FN) mRNA has been shown to be increased in the brain of old rats and during in vivo and in vitro aging of both endothelial cells and fibroblasts, it was of interest to determine,what effect age and caloric restriction have on the ability of liver cells to express FN mRNA. The prevalence of fibronectin mRNA containing the alternatively spliced variant V95 (FN-V95) was examined by RNA gel blot hybridization in the liver of IO-mo, 18-mo, 30-mo ad lib-fed (AL) and 30-mo food-restricted (FR) rats. The transcripts coding for FN-V95 mRNA were well expressed in the liver of IO-mo and 18-mo-old rats. The hybridization signal then increased (1.3-fold, p < .05) in the liver of 30-mo AL rats vs 10-mo-old rats. However, the prevalence of FN-V95 mRNA was dramatically decreased (similar to 4.5-fold, p < .01) in the liver of 30-mo food-restricted rats as compared to 30-mo-old AL rats. The distribution of FN-V95 mRNA was also investigated by non-radioactive in situ hybridization (ISH) on liver frozen sections, The hybridization signal for FN-V95 mRNA was evenly distributed among liver cells of IO-mo and 18-mo-old rats, while weak hybridization signals were sparsely scattered on liver sections derived from 30-mo-old FR rats. In contrast, strong hybridization signals showing a localized distribution were detected on liver sections obtained from 30-mo-old AL rats. Histologic examination of cryostat sections also revealed a massive accumulation of lipid droplets in the liver of 30-mo-old AL rats. Since fibronectin mRNA is mainly contributed by fat-storing cells, sinusoidal endothelial cells and, to a lesser extent, hepatocytes, we conclude that the increased expression of FN-V95 mRNA in the liver of 30-mo-old AL rats is the result of the increase in the number of fat-storing cells in the liver of aged rots. We hypothesize that a reduction in the rate of fibronectin synthesis and incorporation into the extracellular matrix of the liver would render the aged rat liver more susceptible to mechanical damage. These observations are in line with the available data on the aging rat liver.