Ac-SDKP经HSP27调节锌指蛋白而抑制肺上皮细胞-间质转化  

Inhibitory effect of N-acetyl-seryl-aspartyl-lysyl-proline on epithelial-mesenchymal transition by heat-shock protein 27/zinc finger proteins

作　　者：邓海静[1] 李世峰[1] 张丽娟[1] 薛新新 杜世璞 孙月[1] 徐洪[1] 杨方[1] 

机构地区：[1]河北联合大学医学实验研究中心,老年医学国际科技合作基地,河北唐山063000

出　　处：《中国病理生理杂志》2015年第1期1-7,共7页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81072254;No.81302395);河北省高等学校科学技术研究重点项目(No.ZD20131035);唐山市科技计划项目(No.13130299z)

摘　　要：目的:探讨N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸(Ac-SDKP)是否通过抑制热休克蛋白27(heat-shock protein 27,HSP 27)的表达,进而抑制锌指蛋白SNAI1、SNAI2的表达,而发挥阻抑转化生长因子(TGF)-β1诱导的人肺泡Ⅱ型上皮细胞向间质细胞(肌成纤维细胞)的转化以及Ⅰ型、Ⅲ型胶原蛋白的表达。方法:激光共聚焦检测TGF-β1诱导的人肺泡Ⅱ型上皮细胞向肌成纤维细胞转化中HSP27及SNAI1、SNAI2蛋白的共定位表达;real-time PCR法检测HSP27、SNAI1和SNAI2 mRNA的表达;Western blotting法检测HSP27、SNAI1、SNAI2和Ⅰ型、Ⅲ型胶原蛋白的表达,以及转染HSP27干扰质粒后SNAI1、SNAI2蛋白及Ⅰ型、Ⅲ型胶原蛋白表达的变化。结果:与对照组相比,TGF-β1刺激组HSP27、SNAI1、SNAI2及Ⅰ型、Ⅲ型胶原蛋白表达增强;给予Ac-SDKP干预后,HSP27、SNAI1、SNAI2及Ⅰ型、Ⅲ型胶原蛋白表达明显降低,差异有统计学意义。用HSP27的干扰质粒转扰细胞后,SNAI1、SNAI2及Ⅰ型、Ⅲ型胶原蛋白表达降低,其中SNAI1和Ⅰ型、Ⅲ型胶原蛋白的表达与TGF-β1刺激组比较差异有统计学意义。这与Ac-SDKP干预的结果相似。结论:Ac-SDKP能够通过对HSP27表达的调节,降低锌指蛋白SNAI1和SNAI2的表达,进而抑制肺泡Ⅱ型上皮细胞向肌成纤维细胞的转化及胶原蛋白的合成。AIM： To detect whether N-acetyl-seryl-aspartyl-lysyl-proline （Ac-SDKP） inhibits epithelial-mes-enchymal transition in A549 cells induced by TGF-β1 through suppressing the expression of heat shock protein 27 （HSP27） and zinc finger proteins Snail （including SNAI1and SNAI2） which ultimately inhibited the deposition of type I and type III collagens.METHODS：The colocalizations of HSP27 and SNAI1/SNAI2 respectively on A549 alveolar epi-thelial cells induced by TGF-β1 were measured by confocal microscopy .The expression of HSP27, SNAI1 and SNAI2 at mRNA level was detected by real-time PCR.Western blotting analysis was used to detect the expression of HSP 27, SNAI1 and SNAI2 on epithelial-mesenchymal transition in A549 cells induced by TGF-β1 and also the deposition of type I and type III collagens in A549 cells transfected with HSP27shRNA prior to TGF-β1 stimulation.RESULTS： Compared with control group, TGF-β1 increased the expression of HSP27, SNAI1, SNAI2, type I and type III collagen, which decreased significantly followed by Ac-SDKP intervention.The expression of SNAI1, type I and type III collagen decreased signifi-cantly after transfected with HSP27shRNA in A549 cells, which had the similar effect on Ac-SDKP intervention.CON-CLUSION：Ac-SDKP inhibits the transition of cultured A 549 cells to myofibroblasts and attenuates collagen synthesis by＆amp;nbsp;suppressing the expression of HSP 27 and zinc finger proteins SNAI 1 and SNAI2.

关 键 词：N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸 肺泡Ⅱ型上皮细胞 肌成纤维细胞 热休克蛋白27 锌指蛋白SNAI1 锌指蛋白SNAI2 

分 类 号：R329.21[医药卫生—人体解剖和组织胚胎学]