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Dissertation
The role of Syk kinase in UV mediated skin damage
Doctor of Philosophy (Ph.D.), Drexel University
Mar 2011
DOI:
https://doi.org/10.17918/etd-6582
Abstract
Ultraviolet (UV) irradiation is the main cause of skin photo-damage with resulting modulation of matrix metalloproteinases (MMPs) leading to collagen degradation. There is no easily accessible molecular indicator of early skin UV damage. In this study, we investigated the effects of Spleen tyrosine kinase (Syk) 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 or human dermal keratinocytes (HDKs) 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 and HDKs demonstrated that both a Syk inhibitor and Syk siRNA were able to inhibit MMP-1 expression in these cells in response to UV exposure 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 and HDKs. Experiments with hairless mice suggest that Syk expression is an earlier indicator of UV exposure than MMP-13 expression. Furthermore, the results of Syk inhibitor (piceatannol) in hairless mice indicated that MMP-13 expression was reduced in the presence of piceatannol. It suggests that not only Syk expression but its activity is important for the effect on UV induced skin damage. Finally, our data from human biopsies demonstrate that elevated Syk expression can be found in UV exposed skin compared to skin unexposed to UV. Although the evaluated sample number is not large, the difference is statistically significant. 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.
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Details
- Title
- The role of Syk kinase in UV mediated skin damage
- Creators
- Zhenyu Huang - DU
- Contributors
- Elisabeth S. Papazoglou (Advisor) - DU
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xiii, 109 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems; Drexel University
- Other Identifier
- 6582; 991014632541704721