M. Krupsky et al., REGULATION OF TYPE-I COLLAGEN MESSENGER-RNA BY AMINO-ACID DEPRIVATIONIN HUMAN LUNG FIBROBLASTS, The Journal of biological chemistry, 272(21), 1997, pp. 13864-13868
The steady state levels of alpha 1(I) collagen mRNA are decreased by r
etinoic acid and prostaglandin E-2. These effector substances decrease
the uptake of A system amino acids. We examined the effect of amino a
cid deprivation on the steady state levels of alpha 1(I) collagen in h
uman lung fibroblasts, Maintenance of fibroblasts in amino acid-free m
edium decreased alpha 1(I) collagen mRNA levels by 29% at 24 h and 78%
at 72 h. Frequent refeeding of cultures with amino acid-free medium r
esulted in more rapid decreases in intracellular amino acids and in al
pha 1(I) collagen mRNA levels. The decrease in alpha 1(I) collagen mRN
A levels was mediated by decreases in mRNA stability as assessed by a
half-life determination using actinomycin D and by decreases in the ra
te of transcription as assessed by nuclear run on assay. Treatment of
fibroblasts with medium containing amino acids resulted in rapid resto
ration of alpha 1(I) collagen mRNA levels. This increase in alpha 1(I)
collagen mRNA expression required protein synthesis as determined by
cycloheximide sensitivity and was inhibited by prostaglandin E-2. Thes
e data indicate that alpha 1(I) collagen mRNA levels are sensitive to
alterations in the amount of intracellular amino acids and suggest a p
otential mechanism whereby alpha 1(I) collagen accumulation may be reg
ulated independent of inflammatory mediators following lung injury.