人肾小球系膜细胞增生硬化相关新基因AngRem104的表达和功能研究  

Expression and functional analysis of novel gene AngRem104 associated with glomerular sclerosis

作　　者：梁秀彬[1] 张宏[1] 王海燕[1] 

机构地区：[1]北京大学第一医院肾内科,北京大学肾脏病研究所北京100034

出　　处：《中国病理生理杂志》2003年第8期1016-1020,共5页Chinese Journal of Pathophysiology

基　　金：北京大学人类疾病基因中心科研基金资助项目 (No .A - 2 1) ;国家自然科学基金资助项目 (No.30 170 35 1)

摘　　要：目的 :AngRem10 4 (angiotensinⅡrelatedgenesinmesangialcells)是血管紧张素Ⅱ (AngⅡ )刺激系膜细胞后上调表达的新基因 (GenBank登录号是AF36 7870 )。本研究旨在进一步探讨新基因AngRem10 4的功能 ,为研究肾小球增生硬化可能的分子机制奠定基础。方法 :用Northernblot检测AngRem10 4在正常人组织中的表达分布及其在AngⅡ刺激和刺激被losartan阻断后的表达变化。构建AngRem10 4与pcDNA3 1/V5 /His -TOPO的正义和反义真核表达载体 ,并转染至体外培养人肾小球系膜细胞 ,用RT -PCR的方法检测在AngRem10 4基因过度表达时纤粘连蛋白(FN)的表达变化。通过ExPASy对AngRem10 4进行生物信息学分析。结果 :生物信息学分析提示AngRem10 4是一种核蛋白。Northernblot结果显示AngRem10 4在正常人心脏、胎盘、肝脏、骨骼肌、肾脏和胰腺组织中广泛的表达 ,而在脑组织和肺中未检测到表达。在AngⅡ刺激人系膜细胞后 6h ,AngRem10 4表达明显上调 ,并可持续至 4 8h ,但却剂量依赖地被AngⅡI型受体 (AT1R)拮抗剂 (losartan)抑制。用RT -PCR的方法检测到在AngRem10 4基因过度表达时FN的表达明显上调 ,而当反义阻断AngRem10 4基因的表达时 ,在AngⅡ刺激下人系膜细胞FN的表达无明显改变。结论 :AngRem10 4是在正常人组织内?AIM: To study the expression and function of novel gene AngRem104. METHODS: Northern blot was performed to detect the distribution of AngRem104 in human multiple normal tissues as well as the effect of AngⅡ and AT1R antagonist (losartan) on AngRem104 expression. The sense and antisense eukaryotic expression vectors of AngRem104 were constructed and transfected into human mesangial cells. RT-PCR was used to detect the expression of FN when AngRem104 was over-expressed. Primary sequence and motif analysis of AngRem104 protein were performed by on-line ExPasy predictive tools. RESULTS: AngRem104 was predicted to localize at the cellular nucleus. It was widely expressed in human heart, placenta, liver, muscle, kidney and pancreas. Moreover, the up-regulated expression of AngRem104 induced by AngⅡ was inhibited by losartan in a dose-dependent manner. CONCLUSION: AngRem104 is a novel nuclear protein related to the expression of fibronectin and could be up-regulated by AngⅡ in human MC.

关 键 词：血管紧张素Ⅱ 纤连蛋白类 基因功能 基因 AngRem 肾小球硬化症 病灶性 

分 类 号：R363[医药卫生—病理学]