Epidermal CD147 expression plays a key role in IL-22-induced psoriatic dermatitis.
Epidermal CD147 expression plays a key role in IL-22-induced psoriatic dermatitis.
复制标题
表皮 CD147 表达在 IL-22 诱导的银屑病皮炎中起关键作用。
DOI：
10.1038/srep44172
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发表时间：
2017-03-08
影响因子：
4.6
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Peng C;Zhang S;Lei L;Zhang X;Jia X;Luo Z;Huang X;Kuang Y;Zeng W;Su J;Chen X
银屑病是一种以角质形成细胞增殖和终末分化异常为特征的慢性炎症性皮肤病。白细胞介素-22（IL-22）和转录因子Stat 3在银屑病的发病机制中起关键作用。CD 147是属于免疫球蛋白超家族的跨膜糖基化蛋白。我们以前的研究表明，CD 147是角质形成细胞高度增殖和角质形成细胞分化不良的标志物，也是银屑病易感基因。目前的研究表明，CD 147在银屑病皮损中高度表达。K5启动子转基因小鼠表皮中特异性CD 147过表达促进咪喹莫特（IMQ）诱导的银屑病样炎症，其特征在于棘层、颗粒层损失和炎性细胞浸润。我们还发现，IL-22在体外和体内增加了CD 147的转录，Stat 3直接结合到CD 147启动子的-854和-440之间，这表明银屑病患者的CD 147表达通过Stat 3激活而上调。此外，CD 147敲低显著阻断IL-22介导的Stat 3活化以及IL-22诱导的细胞因子、趋化因子和抗微生物因子表达。总之，这些研究结果表明，CD 147是一种新的和关键的介导的IL-22诱导的银屑病改变在表皮和银屑病患者可能是一个治疗目标。
Psoriasis is a chronic inflammatory skin disease characterized by abnormal keratinocyte proliferation and terminal differentiation. Interleukin-22 (IL-22) and the transcription factor Stat3 play pivotal roles in the pathogenesis of psoriasis. CD147 is a transmembrane glycosylation protein that belongs to the immunoglobulin superfamily. Our previous studies have shown that CD147 is a marker of high keratinocyte proliferation and poor keratinocyte differentiation as well as a psoriasis susceptibility gene. The current study demonstrates that CD147 is highly expressed in psoriatic skin lesions. Specific CD147 over-expression in the epidermis of K5-promoter transgenic mice promotes imiquimod (IMQ)-induced psoriasis-like inflammation characterized by acanthosis, granular layer loss and inflammatory cell infiltration. We also found that IL-22 increases CD147 transcription in vitro and in vivo and that Stat3 binds directly to the CD147 promoter between positions −854 and −440, suggesting that CD147 expression is up-regulated in patients with psoriasis through Stat3 activation. In addition, CD147 knockdown dramatically blocks IL-22-mediated Stat3 activation as well as IL-22-induced cytokine, chemokine and antimicrobial factor expression. Together, these findings show that CD147 is a novel and key mediator of IL-22-induced psoriatic alterations in the epidermis and might be a therapeutic target in patients with psoriasis.