The role of Syk kinase in ultraviolet-mediated skin damage

Abstract

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. 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. 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). 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. 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.