十五肽BPC-157通过p38 MAPK信号通路途径调节人脐静脉内皮细胞的功能

Involvement of p38 MAPK Pathway in BPC-157-Induced Promo tion of Proliferation and Migration in Human Umbilical Vein Endo thelial Cells

目的:初步探究十五肽BPC-157调节人脐静脉内皮细胞(HUVEC)功能的信号通路作用机制。方法:首先利用生物芯片筛选BPC-157参与激活的细胞信号转导通路途径,进而通过real-time PCR证实BPC-157对候选信号通路中相关基因的mRNA表达水平的影响,最后采用Western印迹观察BPC-157对候选信号通路中相关蛋白的磷酸化水平影响。结果:10μg/mL BPC-157作用于HUVEC 24 h后,信号转导通路发现者芯片结果显示,与18条信号转导通路相关的96个关键基因中分别有4个基因的mRNA表达水平上调和下调,其中与MAPK信号通路相关的3个关键基因c-Fos、c-Jun和Egr-1的mRNA表达水平显著性上调;低剂量BPC-157(1μg/mL)作用于HUVEC 12 h后,能够促进早期即刻基因c-Fos、c-Jun和Egr-1的mRNA表达水平;10μg/mL BPC-157作用于HUVEC 30 min后,可明显促进ERK1/2、p38蛋白磷酸化。结论:BPC-157可能通过活化MAPK信号转导通路途径后,激活下游早期即刻基因转录,启动靶基因的表达,从而发挥促进HUVEC增殖、迁移等功能。

Objective： We probe into the pentadecapeptide BPC-157 induced function alterations of human umbili- cal vein endothelial cells（HUVEC） and the underlying mechanism. Methods： First, we screened the BPC-157 re- lated signal pathways by microarray; then, real-time PCR had been executed to affirm that BCP-157 could regu- late several signal molecules expression on mRNA level which involve in the collected signal pathways; at last, the phosphorylation level of the pathways was detected by Western-blot. Results： After 10 p^g/mL BPC-157 treat- ed HUVEC for 24 h, microarray which includes 96 key genes belonged to 18 different pathways showed that 4 genes level had been regulated, c-Fos, c-Jun and Egr-1, three important molecules pertain to MAPK pathway, were significantly up regulated. BPC-157 also could enhance the expression of the three immediate early genes even in a low dosage（1 txg/mL）. The phosphorylated ERK1/2 and p38 all enriched in HUVEC treated by 10 μg/ mL BPC-157 for 30 rain. Conclusion： BPC-157 promotes the proliferation and migration of human umbilical vein endothelial cells may attribute to its activated stimulation of MAPK signal pathway and immediate early genes ex- pression.