STAT3介导血管紧张素Ⅱ诱导的间充质干细胞VEGF生成  

Involvement of signal transducer and activator of transcription 3 in angiotensin Ⅱ-upregulated vascular endothelial growth factor production in mesenchymal stem cells

作　　者：张竞文[1] 胡亮[1] 刘超[1] 王露露[1] 李庆平[1,2] 

机构地区：[1]南京医科大学药理学系 [2]江苏省心血管病分子干预重点实验室,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2012年第7期891-895,共5页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金资助(30973534;81173052)

摘　　要：目的:探讨血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)对骨髓间充质干细胞(mesenchymal stem cells,MSCs)中信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)水平的调节,分析STAT3在AngⅡ诱导MSCs的血管内皮生长因子(vascular endothelial growth factor,VEGF)表达增加中的作用,研究血管紧张素转化酶(angiotensin convertingenzyme,ACE)与AngⅡ刺激诱导的STAT3磷酸化之间的关系。方法:分离培养大鼠MSCs,以AngⅡ处理细胞,并用针对STAT3的小干扰RNA(STAT3 siRNA)或ACE抑制剂卡多普利提前进行干预。用免疫印迹法(Western blot)检测细胞内STAT3磷酸化和ACE表达水平;用Real-time PCR法检测细胞内VEGF mRNA表达水平;用ELISA法检测培养液中VEGF蛋白水平。结果:①在MSCs中,AngⅡ诱导STAT3的磷酸化水平增加;②STAT3 siRNA明显抑制AngⅡ诱导的VEGF表达和分泌;③卡托普利显著抑制了AngⅡ诱导的STAT3磷酸化。结论:在MSCs中,STAT3参与了AngⅡ诱导的VEGF表达,并且AngⅡ诱导的STAT3具有ACE依赖性。Objective：To explore the involvement of signal transducer and activator of transcription 3 （STAT3） in angiotensin Ⅱ （Ang Ⅱ ） induced vascular endothelial growth factor（VEGF） expression and the role of angiotensin converting enzyme （ACE） in regulating STAT3 phosphorylation in mesenchymal stem cells（MSCs）. Methods：STAT3 phosphorylation under Angll stimulation was analyzed by Western blot analysis, siRNA targeting STAT3 （STAT3 siRNA） was used to inhibit STAT3,and its effect on VEGF production was examined by measuring VEGF protein level in conditioned media and VEGF mRNA expression in MSCs with ELISA and real-time PCR,respectively. Besides, captopril was used to specifically inhibit ACE, and its effect on STAT3 phosphorylation was analyzed by Western blot. Results： （1） Ang Ⅱ stimulation significantly increased STAT3 phosphorylation level; （2） Pretreatment with STAT3 siRNA markedly abolished the Ang Ⅱ-induced increase of VEGF mRNA expression and protein synthesis; （2） Captopril significantly inhibited the Ang Ⅱ-induced STAT3 phosphorylation. Conclusion：STAT3 is involved in the Ang Ⅱ-stimulated VEGF expression,and the Ang Ⅱ-induced STAT3 phosphorylation is ACE dependent in MSCs.

关 键 词：骨髓间充质干细胞 血管紧张素Ⅱ 血管内皮生长因子 信号转导和转录激活因子3 血管紧张素转化酶 

分 类 号：R541.4[医药卫生—心血管疾病]