Catalase restores the altered mRNA expression of collagen and matrix metalloproteinases by dermal fibroblasts exposed to reactive oxygen species.

We investigated the effects of reactive oxygen species (ROS) on mRNA expression of proalpha1(I) collagen, proalpha1(III) collagen, matrix metalloproteinases-1 (MMP-1), 72 kDa type IV collagenase (MMP-2), and tissue inhibitor of metalloproteinase (TIMP-1) by normal human dermal fibroblasts in a novel three-dimensional culture. Fibroblasts exposed to ROS generated by the hypoxanthine-xanthine oxidase system revealed an increased mRNA expression of MMP-1 and MMP-2 with a maximum at 48 h and 72 h after exposure. A slight increase in the mRNA level of tissue inhibitor of metalloproteinase (TIMP-1) was observed. Increased protein level of MMP-1 and its collagenolytic activity and gelatinolytic activity of MMP-2 was comfirmed as well. In contrast, a time-dependent suppression of both proalpha1(I) and proalpha1(III) collagen mRNA expression was observed 12 h after ROS treatment with a maximum at 48 h and 72 h. Addition of catalase totally abrogated the ROS-induced alteration of these genes. Superoxide dismutase (SOD) abrogated only the increased mRNA expression of MMP-2. These results indicated that ROS mediates the induction of collagenases as well as the suppression of collagen synthesis by dermal fibroblasts in vitro. The biological alterations in collagen metabolism triggered by ROS may be responsible for the development of certain diseases or pathological changes such as photoaged human skin.