Yu Xiao-Jing, Li Chun-Yang, Dai Hong-Yan, Cai Da-Xing, Wang Ke-Yu, Xu Yong-Hao, Chen La-Mei, Zhou Chun-Lei
Department of Dermatology, Qilu Hospital, University of Shandong, Jinan 250012, China.
Exp Mol Pathol. 2007 Dec;83(3):413-8. doi: 10.1016/j.yexmp.2007.05.002. Epub 2007 May 25.
Abnormalities in several signaling pathways and in the expression and/or activation of different transcription factors in psoriatic keratinocytes have been hypothesized to play a role in the pathophysiology of psoriasis. The mitogen-activated protein kinase (MAPK) cascades are among the best characterized of intracellular signaling pathways, and they play important roles in cell proliferation, differentiation, gene expression, and inflammation. We investigated the expression, activation and distribution of extracellular signal-regulated kinases (ERKs), p38 mitogen-activated protein kinases (p38 MAPK) and c-Jun N-terminal kinases (JNKs), using immunohistochemistry and Western blot in lesional psoriatic skin and normal control skin, to clarify the possible roles of these kinases involved in the pathogenesis of psoriasis. The immunoblot analysis demonstrated that activation of ERK1/2 and p38 MAPK increased in the lesional psoriatic skin. In addition, a significant increase in p-MEK (the upstream activator of ERK), and p-CREB (a downstream transcription factor of active ERK) was also found in our experiment. The immunohistochemical study showed that the levels of phosphorylated ERK1/2 and p38 MAPK were enhanced in lesional psoriatic skin compared with controls. Phosphorylated ERK1/2 and p38 exhibited clear nuclear localization throughout the epidermal part of lesional psoriatic skin. These findings suggested that ERK1/2 and p38 pathways were involved in the pathophysiology of psoriasis.
银屑病角质形成细胞中几种信号通路以及不同转录因子的表达和/或激活异常，被认为在银屑病的病理生理学中发挥作用。丝裂原活化蛋白激酶（MAPK）级联是细胞内信号通路中特征最明确的通路之一，它们在细胞增殖、分化、基因表达和炎症中发挥重要作用。我们使用免疫组织化学和蛋白质印迹法，研究了病变银屑病皮肤和正常对照皮肤中细胞外信号调节激酶（ERKs）、p38丝裂原活化蛋白激酶（p38 MAPK）和c-Jun氨基末端激酶（JNKs）的表达、激活和分布，以阐明这些激酶在银屑病发病机制中的可能作用。免疫印迹分析表明，病变银屑病皮肤中ERK1/2和p38 MAPK的激活增加。此外，在我们的实验中还发现p-MEK（ERK的上游激活剂）和p-CREB（活性ERK的下游转录因子）显著增加。免疫组织化学研究表明，与对照组相比，病变银屑病皮肤中磷酸化ERK1/2和p38 MAPK的水平升高。磷酸化ERK1/2和p38在病变银屑病皮肤的整个表皮部分均表现出明显的核定位。这些发现提示ERK1/2和p38通路参与了银屑病的病理生理学过程。
