Modulation of 72-Kilodalton Type IV Collagenase: DISCUSSION(2)
Vitamin C did not directly deactivate MMP-2 but had an effect on MMP-2 genomic expression as revealed by the Western blots, Northern blots, and run-on assays. Down-regulation of MMP-2 gene expression by vitamin C is exerted at physiologic concentrations if we consider the concentrations in amniotic fluid a good indicator of what is occurring inside the chorioam-nion. A nonspecific effect of vitamin C on gene expression, mediated by changes in the cellular redox potential, may be overruled by the lack of effect of equimolar amounts of glutathione and the parallel observations of no change in p-actin gene expression and increase in type I collagen gene expression.
A model of the effect of vitamin C on extracellular matrix remodeling of the chorioamnion during pregnancy may be proposed: if there is low availability of vitamin C in pregnancy, an increase in activity of MMP-2 may occur, leading to increased collagen degradation and a cumulative loss of the main support of the chorioamnion resulting clinically in PROM. We cannot rule out the possibility that collagen synthesized under low availability of vitamin C has a low hydroxyproline and hydroxylysine content and this means that collagen is intrinsically less resistant. The low mechanical strength of PROM-derived chorioamnion may be understood in terms of a simultaneous effect of the above-mentioned factors. asthma inhalers
PROM has been linked to conditions that prevail in developing countries and that are associated with a low socioeconomic level. A vitamin C-deficient diet during pregnancy could be one explanation for why PROM is more frequent in these countries. In addition, these populations are characterized by increased prevalence of infections, which in turn may induce an extra consumption of ascorbic acid. To validate the role of vitamin C in PROM it is necessary to implement other studies that will complement the significance of these results at levels other than the molecular level.