The effect of transforming growth factor beta on rates of procollagen synthesis and degradation in vitro.
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/micrograms 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 less than 0.005). This study demonstrates a novel mechanism which may contribute to the TGF beta-induced increase in procollagen production by fibroblasts.
McAnulty
R J
RJ
Biochemistry Unit, National Heart and Lung Institute, University of London, U.K.
Campa
J S
JS
Cambrey
A D
AD
Laurent
G J
GJ
D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000032:analysis; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006909:Hydroxyproline / Q000096:biosynthesis; D011347:Procollagen / Q000096:biosynthesis* / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D011347:Procollagen; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D004247:DNA; D006909:Hydroxyproline