MK2 plays an important role for the increased vascular permeability that follows thermal injury
MK2 plays an important role for the increased vascular permeability that follows thermal injury
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MK2 在热损伤后血管通透性增加方面发挥着重要作用。
DOI：
10.1016/j.burns.2012.12.001
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发表时间：
2013-08-01
期刊：
影响因子：
2.7
通讯作者：
Zhao, Ming
中科院分区：
文献类型：
--
作者：
Wu, Wei;Huang, Qiaobing;Zhao, Ming
我们以前报道过Rho激酶参与烧伤引起的血管超通透性。我们进一步研究了Rho激酶的下游信号，发现其特异性抑制剂Y27632显著降低JNK和p38 MAPKs的激活，但对烧伤大鼠血清（burn-serum）诱导的ERK没有作用。发现JNK激活参与热损伤后HUVEC粘附分子的表达，但不参与应力纤维形成过程。通过特异性抑制剂抑制各种MAPKs表明，SB203580 （p38抑制剂），但SP600125 （JNK抑制剂）和PD98059 （ERK抑制剂）都不能消除p38下游激酶MK2的激活。荧光标记的phalloidin对应激纤维的证明表明，MK2的抑制，无论是通过其特异性抑制剂还是显性阴性腺病毒携带构建体，都能显著减少烧伤血清诱导的HUVEC应激纤维的形成，而抑制另一种下游p38 MAPK激酶PEAK则没有这种作用。转染显性阴性腺病毒MK2（Ad-MK2(A)）可显著抑制热损伤诱导的大鼠血管高通透性，并延长热损伤后72 h以上烧伤大鼠的存活时间。这些现象背后的机制之一是Ad-MK2(A)引起烧伤血清诱导的hsp27磷酸化的显著抑制，而腺病毒转运的显性阴性PEAK （Ad-PRAK(A)）不被阻断。虽然通过腺病毒途径阻断MK2的效果还需要进一步的研究和研究替代方法来确定，但我们可能已经发现了热损伤诱导的血管高通透性背后的新途径，即：Rho激酶> p38 > MK2 > HSP27。(C) 2012 Elsevier Ltd和ISBI。版权所有。
We previously reported Rho kinase is involved in vessel hyper-permeability caused by burns. Here we further explore the Rho kinase downstream signaling, it is found that its specific inhibitor Y27632 significantly diminishes the activation of JNK and p38 MAPKs but not ERK that induced by serum from burned rats (burn-serum). JNK activation was found involved in the expression of HUVEC adhesion molecules following thermal injury, although not in the process of stress fiber formation. Inhibition of various MAPKs by specific inhibitors showed that SB203580 (inhibitor of p38), but neither SP600125 (inhibitor of JNK) nor PD98059 (inhibitor of ERK), abolish activation of the p38 downstream kinase MK2. Demonstration of stress fibers by fluorescent-labeled phalloidin showed that inhibition of MK2, either by its specific inhibitor or by dominant negative adeno-viral-carried constructs, significantly reduced burn-serum-induced HUVEC stress-fiber formation, while inhibition of another downstream p38 MAPK kinase, PEAK, had no such effects. Transfection of dominant negative adeno-viral MK2 (Ad-MK2(A)) significantly inhibited thermal injury-induced blood vessel hyper-permeability in rats and, moreover, prolonged the survival of burned rats beyond 72 h following thermal injury. One of the mechanisms behind these phenomena is that Ad-MK2(A) causes a significant depression of burn-serum-induced HSP27-phosphorylation, while the adeno-viral transported dominant negative PEAK (Ad-PRAK(A)) does not block. Although the effect of blockade of MK2 through its adeno-viral approach requires further study and investigation of alternatives to know for sure, we may have found a new pathway behind thermal-injury-induced blood vessel hyper-permeability, namely: Rho kinase > p38 > MK2 > HSP27. (C) 2012 Elsevier Ltd and ISBI. All rights reserved.