摘要
目的 研究IL-6在前列腺增生（benign prostatic hyperplasia,BPH）的基质细胞上诱导急性期蛋白反应元件（APRE）的活化及STAT3的敲除抑制其活化,推测STAT3介导的JAK/STAT信号及其所激活的ARPE可能作为BPH治疗的靶点.方法 建立IL-6刺激的前列腺基质细胞的体外模型,使用商品化的siRNA,利用Fugene HD进行siRNA转染来敲除STAT3,通过WB检测STAT3表达情况和APRE的活化程度.结果 使用IL-6刺激前列腺基质细胞后,荧光素酶的表达增加水平到9倍,JAK2和STAT3的磷酸化显著性增加.STAT3敲除后,通过荧光素酶的活性检测结果可知在IL-6刺激的情况下,APRE的活性从大约8倍的水平下降到不到2倍.这证实了IL-6介导的JAK/STAT信号通路被严重抑制.结论 JAK2和STAT3的活化能激活APRE的表达,STAT3所介导的JAK/STAT信号及其所激活的ARPE可能作为BPH治疗的靶点.
Objective To speculate that JAK/STAT mediated STAT3 signaling and its activation of acute phase proteins may serve as targets for the treatment of benign prostatic hyperplasia （BPH） in the future through the activation of acute phase protein response element （APRE） induced by IL-6 in prostate stromal cells and the APRE activation of the knock-out and inhibition of STAT3 in prostate stromal cells induced by IL-6.Methods A model of prostate stromal cells stimulated by IL-6 in vitro was established.The siRNA was used to detect the expression of STAT3 and the degree of activation of APRE by Fugen HD.The expression of STAT3 and the degree of activation of APRE was detected by WB.Results After using IL-6 to stimulate prostate stromal cells,the expression of luciferase increased to 9 times the level of phosphorylation of JAK2 and STAT3 both had a very large increase.After STAT3 knocked out,the results of luciferase activity detection could be seen,even in the presence of IL-6 stimulation,the activity of APRE decreased from about 8 times to less than 2 times,that is,a decrease of more than 75％.It was also confirmed that all the JAK/STAT signaling pathways in IL-6 were severely inhibited.Conclusions The activation of STAT3 and JAK2 does activate the expression of STAT3,and the JAK/STAT signal mediated by APRE and the acute phase reactive protein are likely to be the targets of BPH therapy in the future.
出处
《国际泌尿系统杂志》
2017年第5期709-713,共5页
International Journal of Urology and Nephrology
基金
四川省科技厅支撑计划（2014SZ0218）
四川省教育厅支撑计划（14ZB0192）
南充市科技局项目（13A0049）
四川省卫生和计划生育委员会科研课题（16PJ204）
关键词
前列腺增生
白细胞介素6
信号传导
Prostatic Hyperplasia
Interleukin-6
Signal Transduction
