Regulation of collagen synthesis.

ABSTRACT

Collagen synthesis is a complex orchestration of intracellular and extracellular events. In addition to synthesis of the polypeptide chains more than a dozen modifications of the molecule occur; most of these are enzymatic and specific for collagen. Regulational control of collagen synthesis promises to be equally complex. Examples are described to 4 specific regulatory influences. Ascorbic acid markedly stimulates collagen synthesis without affecting synthesis of other proteins. This effect appears to be unrelated to its cofactor roles for hydroxylation of lysine and proline. Glucocorticoids at microM concentration specifically inhibit collagen synthesis. Tissues treated with glucocorticoids have diminished levels of mRNA for collagen. During collagen synthesis the aminoterminal propeptide of procollagen is cleaved by a specific protease. This peptide appears to be a feedback inhibitor of collagen synthesis. This effect can be demonstrated in cells and in cell-free synthesizing systems. A membrane receptor system may permit the peptide to be recognized and subsequently act as a translational control mechanism. Viral transformation of fibroblasts results in selectively decreased synthesis of collagen. Levels of cytoplasmic and nuclear mRNA are likewise selectively diminished consistent with transcriptional control.