THE EFFECT OF TRANSFORMING GROWTH-FACTOR-BETA ON RATES OF PROCOLLAGEN SYNTHESIS AND DEGRADATION INVITRO

Transforming growth factor-beta (TGF-beta) is known to stimulate procollagen production and steady-state levels of procollagen mRNAs, but its ability to affect post-translational processing of procollagen has been little studied. This paper demonstrates the application of recently developed ultrasensitive methods for measuring hydroxyproline to assess rates of procollagen synthesis and degradation in vitro with and without TGF-beta. Foetal rat fibroblasts synthesized 8.63 +/- 0.21 pmol hydroxyproline/mu-g DNA per h, which corresponds to approx. 40 molecules of procollagen/cell per s. Addition of TGF-beta to cultures increased total amounts of procollagen synthesized and degraded by 112% and 82%, respectively, but there was a significant decrease in the proportion of procollagen degraded (control, 38.0 +/- 1.1%; TGF-beta, 32.3 +/- 0.9%; P < 0.005). This study demonstrates a novel mechanism which may contribute to the TGF-beta-induced increase in procollagen production by fibroblasts.