组蛋白乙酰化酶对牙周膜干细胞内质网应激激活的调控研究  

Study of histone acetyltransferases regulating endoplasmic reticulum stress of periodontal ligament stem cells

作　　者：薛芃 胡楠[1] 白阳[1] 蔡川 贾婷婷[1] 张贤华[1] XUE Peng;HU Nan;BAI Yang;CAI Chuan;JIA Ting-ting;ZHANG Xian-hua(School of Stomatology,Chinese PLA General Hospital,Beijing 100853,China)

机构地区：[1]解放军总医院第一医学中心口腔科,北京100853

出　　处：《中华老年口腔医学杂志》2020年第2期65-69,75,共6页Chinese Journal of Geriatric Dentistry

基　　金：国家自然科学基金(项目编号:81700968,81500861)。

摘　　要：目的:探讨组蛋白乙酰化酶(histone acetyltransferases,HATs)在人牙周膜干细胞(periodontal ligament stem cells,PDLSCs)中表达以及与内质网应激(endoplasmic reticulum stress,ERs)激活的关系。方法:实时定量PCR筛选HATs在炎症来源牙周膜干细胞(periodontitis periodontal ligament stem cells,P-PDLSCs)中表达情况;使用小干扰RNA(small interfering RNA,siRNA)将筛选出的4个HATs分别抑制,实时定量PCR检测抑制效率和未折叠蛋白反应(unfolded protein response,UPR)相关因子蛋白激酶受体样内质网激酶(protein kinase receptor like ER kinase,PERK)、肌醇需要酶1(inositol requiring enzyme1,IRE1)和转录激活因子6(activating transcription factor 6,ATF6)的表达;透射电镜观察使用小干扰RNA干扰KAT6B(si KAT6B)后内质网形态的变化。结果:与对照组H-PDLSCs相比,4个HATs KAT2A、KAT3B、KAT6A和KAT6B在P-PDLSCs中表达显著降低(分别为0.60±021、0.60±021、0.42±0.26、0.33±0.28),成功检测到四个HATs沉默效率(分别为0.48±0.18、0.37±0.12、0.12±0.23、0.54±0.10)后,发现si KAT6B后PERK表达升高(1.63±0.21)。相比对照组,透射电镜下观察si KAT6B后内质网异常扩张和肿胀。结论:牙周炎症微环境可以引起组蛋白乙酰化酶KAT6B降低,同时引起UPR相关PERK分子激活。Objective:To investigate the expression of histone acetyltransferases(HATs)in human periodontal ligament stem cells(PDLSCs)and their activation with endoplasmic reticulum stress(ERs).Methods:Real-time reverse transcription(RT)-PCR was used to screen the expression of HATs in periodontitis periodontal ligament stem cells(P-PDLSCs).Small interfering RNA(si RNA)was used to suppress the 4 HAT.RT PCR detection of inhibitory efficiency and expression of unfolded protein response(UPR)-related factor protein,kinase receptor-like endoplasmic reticulum kinase(PERK),inositol requiring enzyme 1(IRE1)and activating transcription factor 6(ATF6).The shape and size of ER was examined using a transmission electron microscope(TEM).Results:KAT2 A,KAT3 B,KAT6 A and KAT6 B in group P-PDLSCs were respectively 0.60±0.21、0.60±0.21、0.42±0.26 and 0.33±0.28,which were all lesser than group H-PDLSC.The 4 HATs silencing efficiencies were 0.48±0.18,0.37±0.12,0.12±0.23 and 0.54±0.10,and the expression of PERK was 1.63±0.21,which was increased after si KAT6 B.Compared with H-PDLSCs,our results showed more dilated and abundant ER in P-PDLSCs using a TEM.Conclusions:The periodontal inflammatory microenvironment can lead to the decreased expression of histone acetylase KAT6 B and then the increased of UPR related gene,PERK.

关 键 词：组蛋白乙酰化酶 牙周膜干细胞 炎症微环境 内质网应激 

分 类 号：R781.4[医药卫生—口腔医学]