[1]郭腾飞),轩青霞),吴玉丹),等.GRP78-ATF6-CHOP通路相关分子在葡聚糖硫酸钠诱导的小鼠结肠炎中的表达[J].郑州大学学报(医学版),2019,(06):806-811.[doi:10.13705/j.issn.1671-6825.2018.11.081]
 GUO Tengfei),XUAN Qingxia),WU Yudan),et al.Expressions of GRP78-ATF6-CHOP pathway molecules in colonal tissue of dextran sulphate sodium-induced colitis mice[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2019,(06):806-811.[doi:10.13705/j.issn.1671-6825.2018.11.081]
点击复制

GRP78-ATF6-CHOP通路相关分子在葡聚糖硫酸钠诱导的小鼠结肠炎中的表达()
分享到:

《郑州大学学报(医学版)》[ISSN:1671-6825/CN:41-1340/R]

卷:
期数:
2019年06期
页码:
806-811
栏目:
论著
出版日期:
2019-11-20

文章信息/Info

Title:
Expressions of GRP78-ATF6-CHOP pathway molecules in colonal tissue of dextran sulphate sodium-induced colitis mice
作者:
郭腾飞12)轩青霞1)吴玉丹2)董仕桢2)高 磊1)陈 攀1)常永超2)高 强13)
1)河南科技大学临床医学院; 河南科技大学第一附属医院消化内科 河南洛阳 471003 2)河南科技大学临床医学院; 河南科技大学第一附属医院检验科 河南洛阳 471003 3)首都医科大学附属北京康复医院消化内科 北京 100144
Author(s):
GUO Tengfei12) XUAN Qingxia1) WU Yudan2) DONG Shizhen2) GAO Lei1) CHEN Pan1) CHANG Yongchao2) GAO Qiang13)
1)College of Clinical Medicine,Henan University of Science and Technology; Department of Gastroenterology and Hepatology, the First Affiliated Hospital,Henan University of Science and Technology,Luoyang,Henan,471003 2)College of Clinical Medicine,Henan University of Science and Technology; Department of Clinical Laboratory, the First Affiliated Hospital,Henan University of Science and Technology, Luoyang, Henan,471003 3)Department of Gastroenterology and Hepatology, Beijing Rehabilitation Hospital of Capital Medical University, Beijing, 100144
关键词:
炎症性肠病 葡聚糖硫酸钠 葡萄糖调节蛋白78 活化转录因子6 CHOP 小鼠
Keywords:
inflammatory bowel disease dextran sulphate sodium glucose regulated protein of 78 activating transcription factor 6 C/EBP homologous protein mouse
分类号:
R574.6
DOI:
10.13705/j.issn.1671-6825.2018.11.081
摘要:
目的:探讨GRP78-ATF6-CHOP通路在葡聚糖硫酸钠(DSS)诱导的小鼠结肠炎中的表达及意义。方法:选取6~8周龄的健康清洁级129S1/SvJ种系小鼠,随机分为DSS组和对照组(n=8),DSS组饮用30 g/L DSS溶液,对照组饮用无菌蒸馏水; 于第6天处死小鼠。通过疾病活动指数评分(DAI)、结肠长度测定和HE染色等方法评估小鼠肠道炎症程度,采用qRT-PCR检测小鼠结肠组织中炎症因子IL-1β、IL-6、TNF-α以及内质网应激相关分子葡萄糖调节蛋白78(GRP78)、IRE1α、PERK、活化转录因子6(ATF6)和CHOP mRNA的表达水平,采用免疫组化法和蛋白印迹法检测小鼠结肠组织中GRP78、ATF6和CHOP蛋白的表达。结果:对照组无肠炎表现,DSS组有严重的肠炎表现。与对照组相比,DSS组结肠组织中炎症因子IL-1β、IL-6、TNF-α GRP78、ATF6和CHOP mRNA表达升高(P均<0.001)。免疫组化显示GRP78主要表达于结肠上皮细胞的胞质及胞膜,ATF6主要表达于结肠上皮细胞的胞质及胞核,CHOP主要表达于结肠上皮细胞的胞核中; DSS组GRP78、ATF6和CHOP蛋白表达水平高于对照组(P均<0.001)。结论:GRP78-ATF6-CHOP通路相关分子可能在DSS诱导的小鼠结肠炎的发生、发展中起重要作用。
Abstract:
Aim:To investigate the expressions of endoplasmic reticulum stress(ERS)-related molecules GRP78, ATF6 and CHOP in colonal tissue of dextran sulphate sodium(DSS)-induced colitis mice and analyze their significance in pathogenesis of colitis.Method:Six-to-eight-week-old 129S1/SvJ mice were randomly divided into DSS group and control group(n=8 for each group). Mice in DSS group were given 30 g/L DSS for 6 days. Mice in control group were given diatilled water.Disease Activity Index(DAI), colon length and inflammatory scores of colon were assessed. The mRNA levels of inflammatory cytokines IL-1β, IL-6 and TNF-α, and ERS-related molecules GRP78, IRE1α, PERK, ATF6 and CHOP were measured by qRT-PCR. The protein expressions of GRP78, ATF6 and CHOP in colonal tissue were evaluated by immunohistochemistry and Western blot.Results:There was no colitis in mice of control group, whereas severe colitis in DSS group. In DSS group, IL-1β, IL-6, TNF-α,GRP78,ATF6,CHOP mRNA and GRP78,ATF6,CHOP protein were all increased significantly compared with control group(all P<0.001). GRP78 protein was mainly expressed in cytoplasm and cytomembrane of colonic epithelial cells; ATF6 protein was mainly expressed in the nucleus and cytoplasm of colonic epithelial cells; CHOP protein was mainly expressed in the nucleus of colonic epithelial cells.Conclusion:The activity of GRP78-ATF6-CHOP pathway is involved in the pathogenesis of inflammatory bowel disease.

参考文献/References:

[1] ANANTHAKRISHNAN AN.Epidemiology and risk factors for IBD[J].Nat Rev Gastroenterol Hepatol,2015,12(4):205
[2] MA XS,DAI ZL,SUN KJ,et al.Intestinal epithelial cell endoplasmic reticulum stress and inflammatory bowel disease pathogenesis: an update review[J].Front Immunol,2017,8:1271
[3] SANO R,REED JC.ER stress-induced cell death mechanisms[J].Biochim Biophys Acta,2013,1833(12):3460
[4] CHONG WC,SHASTRI MD,ERI R.Endoplasmic reticulum stress and oxidative stress: a vicious nexus implicated in bowel disease pathophysiology[J].Int J Mol Sci,2017,18(4):pii:E771
[5] CAO SS,KAUFMAN RJ.Endoplasmic reticulum stress and oxidative stress in cell fate decision and human disease[J].Antioxid Redox Signal,2014,21(3):396
[6] LUO K,CAO SS.Endoplasmic reticulum stress in intestinal epithelial cell function and inflammatory bowel disease[J].Gastroenterol Res Pract,2015.doi: 10.1155/2015/328791
[7] LI Y,GUO Y,TANG J,et al.New insights into the roles of CHOP-induced apoptosis in ER stress[J].Acta Biochim Biophys Sin(Shanghai),2014,46(8):629
[8] JACKSON LN,ZHOU Y,QIU S,et al.Alternative medicine products as a novel treatment strategy for inflammatory bowel disease[J].Am J Chin Med,2008,36(5):953
[9] ESWORTHY RS,KIM BW,LARSON GP,et al.Colitis locus on chromosome 2 impacting the severity of early-onset disease in mice deficient in GPX1 and GPX2[J].Inflamm Bowel Dis,2011,17(6):1373
[10]陈梦露,董仕桢,常永超,等.5-羟色胺对肠炎小鼠结肠组织中GRP78表达的影响[J].郑州大学学报(医学版),2016,51(2):171
[11] VEGH Z, KURTI Z, LAKATOS PL.Epidemiology of inflammatory bowel diseases from west to east[J]. J Dig Dis,2017,18(2):92
[12]MALIK TA.Inflammatory bowel disease:historical perspective,epidemiology,and risk factors[J].Surg Clin North Am,2015,95(6):1105
[13]尹跃霏,陈亚丽,李赟, 等.细胞内镜在炎症性肠病诊治中的应用进展[J].解放军医学杂志,2018,43(11):983
[14]MEI Y,THOMPSON MD,COHEN RA,et al.Endoplasmic reticulum stress and related pathological processes[J].J Pharmacol Biomed Anal,2013,1(2):1000107
[15]HILLARY RF,FITZGERALD U.A lifetime of stress: ATF6 in development and homeostasis[J].J Biomed Sci,2018,25(1):48
[16]刘亮,肖延风,尹春燕,等.内质网应激在高脂饲料诱导幼年大鼠脂肪性肝损伤中的作用[J].西安交通大学学报(医学版),2015,36(6):724
[17]TRETON X,PEDRUZZI E,CAZALS-HATEM DA,et al.Altered endoplasmic reticulum stress affects translation in inactive colon tissue from patients with ulcerative colitis[J].Gastroenterology,2011,141(3):1024
[18]HANAOKA M,ISHIKAWA T,ISHIGURO M,et al.Expression of ATF6 as a marker of pre-cancerous atypical change in ulcerative colitis-associated colorectal cancer: a potential role in the management of dysplasia[J].J Gastroenterol,2018,53(5):631
[19]王白燕,韩倩倩,朱艳琴,等.GRP78、CHOP在α-细辛醚诱导的Eca109细胞凋亡中的作用[J].郑州大学学报(医学版),2017,52(2):109
[20]XU WL,LU XY,ZHENG JW,et al.Melatonin protects against neuronal apoptosis via suppression of the ATF6/CHOP pathway in a rat model of intracerebral hemorrhage[J].Front Neurosci,2018,12:638

相似文献/References:

[1]仝亚林,杨万荷,李家群,等.炎症性肠病小鼠外周血和结肠上皮组织中CD98蛋白的表达*[J].郑州大学学报(医学版),2013,(05):599.
 TONG Yalin,YANG Wanhe,LI Jiaqun,et al.Expression of CD98 protein in peripheral blood and colonic epithelial tissue of mice with inflammatory bowel disease[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2013,(06):599.
[2]李治国,江红艳,李林静,等.结肠炎小鼠外周血和结肠上皮组织中Gal9的表达*[J].郑州大学学报(医学版),2015,(01):68.
 LI Zhiguo,JIANG Hongyan,LI Linjing,et al.Expression of Gal9 in peripheral blood and colonic epithelial tissue of mice with colitis[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2015,(06):68.

备注/Memo

备注/Memo:
【基金项目】国家自然科学基金项目(81370487) 【作者简介】高强,通信作者,男,1961年8月生,博士,主任医师,研究方向:消化道炎症与肿瘤,E-mail:gaoq@ccmu.edu.cn
更新日期/Last Update: 2019-11-20