Topically applied vitamin C enhances the mRNA level of collagens I and III, their processing enzymes and tissue inhibitor of matrix metalloproteinase1 in the human dermis

Ascorbic acid (vitamin C) is a cofactor required for the function of severa l hydroxylases and monooxygenases. It is not synthesized in humans and some other animal species and has to be provided by diet or pharmacologic means . Its absence is responsible for scurvy, a condition related in its initial phases to a defective synthesis of collagen by the reduced function of pro lylhydroxylase and production of collagen polypeptides lacking hydroxyproli ne, therefore, they are unable to assemble into stable triple-helical colla gen molecules. In fibroblast cultures, vitamin C also stimulates collagen p roduction by increasing the steady-state level of mRNA of collagen types I and III through enhanced transcription and prolonged half-life of the trans cripts. The aim of the experimental work has been to evaluate the effect on dermal cells of a preparation of vitamin C topically applied on one side a s placebo on the other side of the dorsal face of the upper forearm of post menopausal women. Biopsies were collected on both sides and the level of mR NA measured by non competitive reverse transcription-polymerase chain react ion made quantitative by the simultaneous transcription and amplification o f synthetic RNA used as internal standards. The mRNA of collagen type I and type III were increased to a similar extent by vitamin C and that of three post-translational enzymes, the carboxy- and amino-procollagen proteinases and lysyloxidase similarly increased. The mRNA of decorin was also stimula ted, but elastin, and fibrillin 1 and 2 were not modified by the vitamin. T he expression of matrix metalloproteinases 1, 2, and 9 was not significantl y changed, but an increased level of tissue inhibitor of matrix metalloprot einase 1 mRNA was observed without modification of tissue inhibitor of matr ix metalloproteinase 2 mRNA. The stimulating activity of topical vitamin C was most conspicuous in the women with the lowest dietary intake of the vit amin and unrelated to the level of actinic damage. The results indicate tha t the functional activity of the dermal cells is not maximal in postmenopau sal women and can be increased.