The role of Syk kinase in ultraviolet-mediated skin damage.
The role of Syk kinase in ultraviolet-mediated skin damage.
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DOI：
10.1111/j.1365-2133.2011.10309.x
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发表时间：
2011-07
期刊：
影响因子：
--
通讯作者：
Uitto J
中科院分区：
文献类型：
--
作者：
Papazoglou E;Huang ZY;Sunkari C;Uitto J
紫外线照射是皮肤光损伤的主要原因;基质金属蛋白酶（MMPs）的调节导致胶原蛋白降解。没有容易获得的早期皮肤紫外线损伤的分子指标。在这项研究中，我们研究了Syk激酶对MMP表达的影响，并评估了Syk作为皮肤紫外线损伤早期指标的敏感性和实用性。用Syk cDNA转染人真皮成纤维细胞（HDF）以过表达Syk。UV照射后，用Western blot法检测MMP-1表达和Syk活性。通过Syk siRNA或选择性Syk抑制剂进一步探索Syk对HDF中MMP-1表达的影响。还在UV暴露后的HDF中评价了Syk的可能下游分子。在体内（MMP-13，无毛小鼠）进一步探索Syk和胶原酶之间的关系。我们在HDFs中的研究表明，Syk抑制剂和Syk siRNA都能够抑制暴露于UV的HDFs中MMP-1的表达，并且Syk的过表达增加MMP-1的表达和JNK激酶的活性，但不增加p38或Erk 1/2 MAP激酶的活性。紫外线照射增强HDFs中Syk的表达和活性。用无毛小鼠进行的实验表明，Syk表达是比MMP-13表达更早的紫外线暴露指标。我们的研究结果表明，Syk的表达与MMP（MMP-1在人类和MMP-13在小鼠）的增加，在响应紫外线照射。这些发现表明Syk可能是通过调节MMPs来预防和治疗皮肤光损伤的新靶点。
UV irradiation is the main cause of skin photo-damage; 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.
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影响因子：
3.6
作者：
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通讯作者：
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