Role of VEGF receptors in normal and psoriatic human keratinocytes: evidence from irradiation with different UV sources.
Role of VEGF receptors in normal and psoriatic human keratinocytes: evidence from irradiation with different UV sources.
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VEGF 受体在正常和银屑病人类角质形成细胞中的作用：来自不同紫外线源照射的证据
DOI：
10.1371/journal.pone.0055463
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zheng M
中科院分区：
文献类型：
--
作者：
Zhu JW;Wu XJ;Lu ZF;Luo D;Cai SQ;Zheng M
血管内皮生长因子(VEGF)促进血管生成，在生理和病理条件下都发挥着重要作用。血管内皮生长因子受体(VEGFRs)是血管内皮生长因子的高亲和力受体，最初被认为是内皮细胞的特异性受体。我们先前报道，VEGFRs在正常人角质形成细胞中也有结构性表达，在银屑病表皮中高表达。此外，UVB还可以激活正常角质形成细胞中的VEGFRs，激活的VEGFR-2信号参与了促生存机制。在这里，我们发现，在正常人角质形成细胞中，VEGFRs也被UVA通过PKC上调和激活，有趣的是，激活的VEGFR-1和VEGFR-2都能保护UVA诱导的细胞死亡。由于VEGFRs在银屑病表皮中过度表达，我们进一步研究了窄带UVB(NB-UVB)光疗或外用0.05%一水卤米松乳膏对其表达的影响。令人惊讶的是，两种治疗方法都显著减弱了银屑病患者表皮中过度表达的血管内皮生长因子受体。在NB-UVB治疗期间，VEGFRs首先在银屑病底部下降，然后在上部逐渐下降。银屑病皮损中VEGFRs被激活，NB-UVB可增强其活性，但整体治疗后检测不到VEGFRs。这一过程与卤米松非常不同，在卤米松中，VEGFRs和磷酸化VEGFRs以渐进、均匀的方式减少。我们的发现进一步表明，紫外线诱导的VEGFRs的激活对角质形成细胞来说是一个促进生存的信号。此外，VEGFRs可能参与了银屑病的病理过程，紫外线光疗通过直接调节VEGFRs的表达而有效治疗银屑病。
Vascular endothelial growth factor (VEGF) promotes angiogenesis and plays important roles both in physiological and pathological conditions. VEGF receptors (VEGFRs) are high-affinity receptors for VEGF and are originally considered specific to endothelial cells. We previously reported that VEGFRs were also constitutively expressed in normal human keratinocytes and overexpressed in psoriatic epidermis. In addition, UVB can activate VEGFRs in normal keratinocytes, and the activated VEGFR-2 signaling is involved in the pro-survival mechanism. Here, we show that VEGFRs were also upregulated and activated by UVA in normal human keratinocytes via PKC, and interestingly, both the activated VEGFR-1 and VEGFR-2 protected against UVA-induced cell death. As VEGFRs were over-expressed in psoriatic epidermis, we further investigated whether narrowband UVB (NB-UVB) phototherapy or topical halomethasone monohydrate 0.05% cream could affect their expression. Surprisingly, the over-expressed VEGFRs in psoriatic epidermis were significantly attenuated by both treatments. During NB-UVB therapy, VEGFRs declined first in the basal, and then gradually in the upper psoriatic epidermis. VEGFRs were activated in psoriatic epidermis, their activation was enhanced by NB-UVB, but turned undetectable after whole therapy. This process was quite different from that by halomethasone, in which VEGFRs and phospho-VEGFRs decreased in a gradual, homogeneous manner. Our findings further suggest that UV-induced activation of VEGFRs serves as a pro-survival signal for keratinocytes. In addition, VEGFRs may be involved in the pathological process of psoriasis, and UV phototherapy is effective for psoriasis by directly modulating the expression of VEGFRs.
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影响因子：
8
作者：
Arun, S. N.;Kaddour-Djebbar, I.;Shapiro, B. A.;Bollag, W. B.
通讯作者：
Bollag, W. B.
影响因子：
82.9
作者：
Carmeliet, P;Moons, L;Persico, MG
通讯作者：
Persico, MG
影响因子：
4.8
作者：
He, YY;Huang, JL;Chignell, CF
通讯作者：
Chignell, CF
DOI：
10.1084/jem.180.3.1141
发表时间：
1994-09-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Detmar M;Brown LF;Claffey KP;Yeo KT;Kocher O;Jackman RW;Berse B;Dvorak HF
通讯作者：
Dvorak HF
影响因子：
7.4
作者：
Lee, Eun-Jung;Jeon, Myung-Shin;Kim, Tae-Yoon
通讯作者：
Kim, Tae-Yoon