Abstract
BACKGROUND: Ultraviolet (UV) irradiation is the main cause of skin photodamage; the resulting modulation of matrix metalloproteinases (MMPs) leads to collagen degradation. There is no easily accessible molecular indicator of early skin UV damage. OBJECTIVES: In this study, we investigated the effects of Syk kinase on MMP expression and evaluated the sensitivity and usefulness of Syk as an early indicator of skin UV damage. METHODS: Human dermal fibroblasts (HDFs) were transfected with Syk cDNA to overexpress Syk. MMP-1 expression and Syk activity were determined by Western blot after UV exposure. The effect of Syk on MMP-1 expression in HDFs was further explored by either Syk siRNA or a selective Syk inhibitor. Possible downstream molecules of Syk were also evaluated in HDFs upon UV exposure. The relationship between Syk and collagenase was further explored in vivo (MMP-13, hairless mice). RESULTS: Our studies in HDFs demonstrated that both a Syk inhibitor and Syk siRNA were able to inhibit MMP-1 expression in HDFs exposed to UV and that overexpression of Syk increased MMP-1 expression and the activity of JNK kinase, but not p38 or Erk1/2 MAP kinase. UV exposure enhanced both expression and activity of Syk in HDFs. Experiments with hairless mice suggested that Syk expression is an earlier indicator of UV exposure than MMP-13 expression. CONCLUSIONS: Our results demonstrate that Syk expression correlates well with increase of MMPs (MMP-1 in humans and MMP-13 in mice) in response to UV exposure. The findings suggest that Syk may be a novel target for the prevention and treatment of skin photodamage by modulating MMPs.