Modulation of 72-Kilodalton Type IV Collagenase (Matrix Metalloproteinase-2) by Ascorbic Acid in Cultured Human Amnion-Derived Cells

Extensive research has been done to investigate the effects of nutrients on placental and fetal development. It is now evident that environmental factors such as diet may exert a profound effect on gene expression during pregnancy. A low intake of vitamin C during pregnancy has been linked to a higher risk of premature rupture of the membranes (PROM) because of its well-known role in collagen biosynthesis. Here we report a new effect of ascorbic acid acting as a modulator of the 72-kDa type IV collagenase (matrix metalloproteinase-2; MMP-2). MMP-2 expression/activity is down-regulated by vitamin C in human amnion cultured cells. The regulatory effect is exerted at the transcriptional level and is specific for MMP-2. Matrix metalloproteinases are implicated in tissue remodeling, and our results allow us to suggest a molecular mechanism that relates poor availability of vitamin C during pregnancy and the development of PROM.