Zhou Chun-Lei, Yu Xiao-Jing, Chen La-Mei, Jiang Hong, Li Chun-Yang
Department of Dermatology, Qilu Hospital, Shandong University, Jinan 250012, PR China.
Regul Pept. 2010 Feb 25;160(1-3):115-20. doi: 10.1016/j.regpep.2009.10.001. Epub 2009 Oct 20.
Corticotropin-releasing hormone (CRH) is a central component of the local hypothalamic-pituitary-adrenal (HPA) axis, which has a functional equivalent in the skin. To determine whether CRH and its receptor, CRH-R1, modulate the expression of vascular endothelial growth factor (VEGF), which is overexpressed in psoriatic epidermis and plays a causal role in the pathogenesis of psoriasis, we investigated the effect of CRH on the expression of VEGF in a human keratinocyte cell line (HaCaT) and whether this effect is via the mitogen-activated protein kinase (MAPK) signal transduction pathways.
Real-time RT-PCR, ELISA assay and western blot were used in the present study to investigate the expression of VEGF in CRH-treated HaCaT cells.
The mRNA and protein levels of VEGF in CRH-treated HaCaT cells were significantly attenuated. However, this downregulation was abrogated by pretreatment with antalarmin, SB203580 and SP600125; pretreatment with PD98059 did not attenuate the effects of CRH on the expression of VEGF. In addition, CRH treatment induced rapid phosphorylation of p38 MAPK and JNK1/2, and antalarmin, SB203580 and SP600125 inhibited CRH-induced phosphorylation of p38 MAPK and JNK1/2.
CRH might downregulate the expression of VEGF through the CRH-R1 and MAPK (p38 MAPK and JNK1/2) signaling pathways in human HaCaT cells.
促肾上腺皮质激素释放激素（CRH）是局部下丘脑 - 垂体 - 肾上腺（HPA）轴的核心组成部分，其在皮肤中有功能等效物。为了确定CRH及其受体CRH - R1是否调节血管内皮生长因子（VEGF）的表达（VEGF在银屑病表皮中过表达并在银屑病发病机制中起因果作用），我们研究了CRH对人角质形成细胞系（HaCaT）中VEGF表达的影响，以及这种影响是否通过丝裂原活化蛋白激酶（MAPK）信号转导途径。
本研究采用实时RT - PCR、ELISA检测和蛋白质印迹法来研究CRH处理的HaCaT细胞中VEGF的表达。
CRH处理的HaCaT细胞中VEGF的mRNA和蛋白质水平显著降低。然而，安他拉明、SB203580和SP600125预处理可消除这种下调；PD98059预处理并未减弱CRH对VEGF表达的影响。此外，CRH处理诱导p38 MAPK和JNK1/2快速磷酸化，而安他拉明、SB203580和SP600125抑制CRH诱导的p38 MAPK和JNK1/2磷酸化。
CRH可能通过CRH - R1和MAPK（p38 MAPK和JNK1/2）信号通路下调人HaCaT细胞中VEGF的表达。
