Hypoxic conditions decrease the mRNA expression of proα1(I) and (III) collagens and increase matrix metalloproteinases-1 of dermal fibroblasts in three-dimensional cultures

The effect of hypoxia on the expression of extracellular matrix-related genes by human dermal fibroblasts was investigated using a novel three-dimensional culture supplemented with L-ascorbic acid 2-phosphate. Experiments were performed by placing replicate dishes in either hypoxic (2%) or in normoxic (20%) condition for various periods of time ranging up to 72 h. The mRNA expression levels of pro alpha1(I), pro alpha1(III) collagens and MMP-1 were analyzed using Northern blotting. Hypoxia transiently increased pro alpha1(I) and pro alpha1(III) collagen gene expression at 24 h, but a prolonged exposure to hypoxia decreased them. A slight increase in MMP-1 mRNA was observed at 24 h and prolonged exposure for up 72 h resulted in significantly increased expression of MMP-1 gene. Our results suggest that enhanced degradation as well as decreased synthesis of collagens induced by hypoxia may account for the delayed wound healing associated with circulatory disturbances. (C) 2000 Published by Elsevier Science Ireland Ltd.