Abstract
Earlier work from our laboratory had shown that vitamin A-deficient rats had increased levels of fibronectin in their serum. To explain this result, we investigated the mechanism whereby vitamin A deficiency affects the production of fibronectin by liver and hepatocytes, since liver is the known source of plasma fibronectin. By use of cDNA specific for rat liver fibronectin, we showed that livers of vitamin A-deficient rats had a 2-4-fold increase in the level of fibronectin mRNA and also a higher transcription rate. Rate of synthesis and secretion of fibronectin was found to be increased 2-fold in primary cultures of hepatocytes of deficient animals. Exogenous addition of retinyl acetate or retinoic acid to the media reversed this increase to control levels. The increase was paralleled by an increase in fibronectin mRNA, also reversed by exogenous retinoic acid. At least 12 h were needed for this reversal to take place. Thus, vitamin A appears to regulate the synthesis of fibronectin through its action on fibronectin mRNA transcription. This represents the first reported observation of an action of vitamin A at the genomic level on the synthesis of a specific protein in liver.
Highlights
Earlier work from our laboratory had shown that of other keratins, adducible to changes in mRNA vitamin A-deficient rats had increased levels of fibro- coding for these proteins
Results presented here show increased rates of fibronectin production by hepatocytes prepared from vitamin A-deficient rats
The observation that thesynthesis of some but not all proteins is affectedby vitamin A deficiency is not surprising: the rate of synthesis of some proteins such as retinol-binding protein remains unchanged, its secretion rate is affected by vitamin A deficiency [25].The modulation of fibronectin synthesis by exogenousaddition of RAor retinyl acetate furtherconfirmed the specific effect of vitamin A deficiency on fibronectin synthesis
Summary
In agreement with results obtained for the absolute values of fibronectin synthesis, 5cm vitamin A-deficient hepatocytes showed an increased synthesis rate (about 2.6-fold) in terms of percentage of total labeled trichloroacetic acid-precipitable protein. B, for long-term incubations, acid-precipitable protein radioactivity was not affected by the hepatocytes from vitamin A-deficient and pair-fed control rats were retinoid. Soprano found in a very limited number of experiments that the transcription rate of the RBP gene in rat liver isolated nuclei using the human RBP cDNA plasma clone in runoff transcription assays could not be quantitated.Our resultfsrom the transcriptionrunoff assay suggest that theincreased level of fibronectin mRNAin vitamin A-deficient liver is due to an increased rate of transcription.
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