Notch通路调控KLF4在糖尿病肾病进展中的作用  

Notch pathway regulates KLF4 in the progression of diabetic nephropathy

作　　者：王晓梅[1] 姚敏[2] 修小斐 王雅琪[2] 陈婷婷 高峰[1] Wang Xiao-mei;Yao Min;Xiu Xiao-fei;Wang Ya-qi;Chen Ting-ting;Gao Feng(Department of Pathology,The Third Hospital of Hebei Medical University,Shijiazhuang 050051,China;Department of Biochemistry,Hebei Medical University,Shijiazhuang 050017,China)

机构地区：[1]河北医科大学第三医院病理科,河北石家庄050051 [2]河北医科大学生物化学研究室,河北石家庄050017

出　　处：《四川生理科学杂志》2021年第9期1478-1481,共4页Sichuan Journal of Physiological Sciences

基　　金：河北省自然科学基金(编号:H2019206045);。

摘　　要：目的:探讨Notch通路通过调控Krüppel样因子4(Krüppel-like factor 4,KLF4)在糖尿病肾病进展中的作用。方法:选取8周龄雄性db/db小鼠作为糖尿病模型,分成db/db组和db/db+γ-分泌酶抑制剂DAPT组(n=6),分别腹腔注射二甲基亚砜(dimethyl sulfoxide,DMSO)和DAPT 10 mg•kg^(-1),每日一次,从第9 w开始连续给药8 w。另选8周龄雄性db/m小鼠作为对照(n=6)。于第16 w分别采用免疫组化检测Nephrin蛋白表达,Western blot检测Notch1、Notch胞内域1(Notch intracellular domain 1,NICD1)、KLF4和Nephrin蛋白表达,Real-time PCR检测Notch1、KLF4和Nephrin mRNA表达。结果:与db/m组相比,db/db组小鼠肾组织Notch1和NICD1表达增加,KLF4和Nephrin表达降低(P<0.01);DAPT抑制Notch通路活化后,增加KLF4和Nephrin表达(P<0.01或P<0.05)。结论:Notch通路通过KLF4调控糖尿病肾病肾组织损伤。Objective:To investigate the effect of Notch pathway on the progression of diabetic nephropathy through regulating Krüppel-like factor 4(KLF4).Methods:The 8 w old male db/db mice were used as diabetic model,which were divided into db/db group and db/db+γ-secretase inhibitor DAPT group with 6 mice in each group.Mice in db/db group and db/db+DAPT group were intraperitoneally injected with dimethyl sulfoxide(DMSO)and DAPT(10 mg•kg^(-1))once a day for 8 w from the 9th w,respectively.The 8 w old male db/m mice were used as control(n=6).At the 16th w,the expression of Nephrin protein was detected by immunohistochemistry.Western blot was used to detect the protein expression of Notch1,Notch intracellular domain 1(NICD1),KLF4 and Nephrin.The mRNA levels of Notch1,KLF4 and Nephrin were determined by Real-time PCR.Results:Compared with db/m group,the expressions of Notch1 and NICD1 in db/db group were increased,while the expressions of KLF4 and Nephrin were decreased(P<0.01).After DAPT inhibited the activation of Notch pathway,the expression of KLF4 and Nephrin increased(P<0.01 or P<0.05).Conclusion:Notch pathway regulates renal injury in diabetic nephropathy through KLF4.

关 键 词：糖尿病肾病 NOTCH通路 Krüppel样因子4 NEPHRIN 

分 类 号：R73[医药卫生—肿瘤]