Regulation of type I collagen mRNA translation by TGF-beta.

We found that TGF-beta caused a sustained increase in type I collagen production up to 48 hr after addition to human lung fibroblast cultures. Northern analysis demonstrated that although TGF-beta increased alpha 1(I) mRNA levels 4-fold at 24 hr and 3-4-fold at 48 hr after addition to cultures, there were minimal or no effects on alpha 2(I) mRNA levels at these time points. In vitro translation of RNA derived from TGF-beta-stimulated cells yielded a 2-3-fold increase in the amount of alpha 2(I) peptide when compared with the in vitro translation of RNA from unstimulated cells. Taken together, these studies showed that TGF-beta increased the translatability of the alpha 2(I) transcript. To examine whether increased translatability of the alpha 2(I) transcript resulted from structural changes in the 5' and 3' untranslated regions, primer extension and S1 nuclease protection assays were employed. These studies demonstrated no gross structural changes in the untranslated regions of the alpha 2(I) transcript induced by TGF-beta-stimulation. Overall, our results suggest the presence of a TGF-beta-regulatable factor which controls translation of type I collagen mRNAs.