Post-transcriptional inhibition of collagen and fibronectin synthesis by a synthetic homolog of a portion of the carboxyl-terminal propeptide of human type I collagen.
We evaluated the effects of a synthetic copy of a highly conserved portion (residues 225-246) of the COOH-propeptide of human pro-alpha 2(I) procollagen on collagen, fibronectin, and total protein synthesis by human fibroblasts. Incubation of COOH-propeptide 225-246 with fibroblasts resulted in a concentration-dependent inhibition of both type I procollagen and fibronectin when compared with controls; a 50% inhibition of both fibronectin and type I collagen was observed at a concentration of 45 microM. Since the overall cellular protein synthesis was only minimally affected, COOH-propeptide appeared to specifically inhibit collagen and fibronectin synthesis. The peptide was nontoxic to cells and the inhibition was completely reversible upon removal of the peptide. We measured the steady-state levels of mRNAs coding for procollagen, fibronectin, and beta-actin by hybridization to specific recombinant cDNA probes; there was no significant change in the steady-state level of mRNAs of the three proteins. These results strongly suggest that the biosynthesis of procollagen and fibronectin in COOH-propeptide-treated cells is inhibited at a post-transcriptional level. These data establish a link between collagen and fibronectin synthesis and further define the important interaction of these molecules in the formation of the extracellular matrix.
D000595:Amino Acid Sequence; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003094:Collagen / Q000096:biosynthesis*; D005347:Fibroblasts / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000494:pharmacology; D011347:Procollagen / Q000138:chemical synthesis* / Q000494:pharmacology; D014158:Transcription, Genetic
D005353:Fibronectins; D010446:Peptide Fragments; D011347:Procollagen; D003094:Collagen