Effect of dextran on synthesis, secretion and deposition of type III procollagen in cultured human fibroblasts.
When subconfluent cultures of primary human skin fibroblasts are incubated for 20 h in the presence of 5% neutral dextran, the newly synthesized procollagens are shifted from the medium into the pericellular matrix fraction. This is accompanied by an overall decrease by 30-50% in the secretion rates of these proteins, as indicated by the incorporation of tritiated proline into collagenase-sensitive macromolecules and by radioimmunoassays for the propeptide regions of type I and III procollagens. Inhibition of tyrosine sulphation in newly formed type III procollagen by NaClO3 does not change the distribution of this protein between the medium and matrix fractions either in the presence or in the absence of the polymer. Processing of type III procollagen at its N-terminus is incomplete in this situation, irrespective of whether the protein is present mainly in the medium or in the pericellular matrix. The concentrations of the mRNAs for the pro alpha 1(I)- and pro alpha 1(III)-chains of procollagens and for actin were monitored for up to 20 h; in the dextran-treated cultures these are not different from the corresponding concentrations in control cultures, indicating that the rapid down-regulation of the synthesis of type I and III procollagens in response to the enhanced pericellular matrix deposition induced by dextran is not due to transcriptional mechanisms.
Jukkola
A
A
Department of Medical Biochemistry, University of Oulu, Finland.
Risteli
J
J
Risteli
L
L
D015152:Blotting, Northern; D003094:Collagen / Q000096:biosynthesis* / Q000378:metabolism; D004247:DNA / Q000235:genetics; D015342:DNA Probes; D003911:Dextrans / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D011233:Precipitin Tests; D011347:Procollagen / Q000096:biosynthesis* / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000187:drug effects / Q000378:metabolism
D015342:DNA Probes; D003911:Dextrans; D011347:Procollagen; D011498:Protein Precursors; D012333:RNA, Messenger; D003094:Collagen; D004247:DNA