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Notch信号通路介导血小板源生长因子AA诱导的血管平滑肌细胞增殖和迁移
引用本文:王金祥,周芳,朱光旭,刘菊芬,朱向情,康华莉,庞荣清,黄岚,潘兴华. Notch信号通路介导血小板源生长因子AA诱导的血管平滑肌细胞增殖和迁移[J]. 中国动脉硬化杂志, 2016, 24(9): 882-888
作者姓名:王金祥  周芳  朱光旭  刘菊芬  朱向情  康华莉  庞荣清  黄岚  潘兴华
作者单位:成都军区昆明总医院细胞生物治疗中心 云南省细胞生物医药技术国家地方联合实验室,云南省昆明市 650032;成都军区昆明总医院细胞生物治疗中心 云南省细胞生物医药技术国家地方联合实验室,云南省昆明市 650032;昆明医科大学成都军区昆明总医院临床学院,云南省昆明市 650032;成都军区昆明总医院细胞生物治疗中心 云南省细胞生物医药技术国家地方联合实验室,云南省昆明市 650032;成都军区昆明总医院细胞生物治疗中心 云南省细胞生物医药技术国家地方联合实验室,云南省昆明市 650032;成都军区昆明总医院细胞生物治疗中心 云南省细胞生物医药技术国家地方联合实验室,云南省昆明市 650032;第三军医大学新桥医院全军心血管疾病研究所,重庆市 430037;成都军区昆明总医院细胞生物治疗中心 云南省细胞生物医药技术国家地方联合实验室,云南省昆明市 650032;第三军医大学新桥医院全军心血管疾病研究所,重庆市 430037;成都军区昆明总医院细胞生物治疗中心 云南省细胞生物医药技术国家地方联合实验室,云南省昆明市 650032
基金项目:国家自然科学基金(81170316)资助
摘    要:目的探讨Notch信号通路在血小板源生长因子AA(PDGF-AA)诱导血管平滑肌细胞(VSMC)增殖和迁移中的作用及机制。方法脱臼处死1~2月龄雄性SD大鼠,无菌取腹主动脉,剥弃外膜及去除内皮后,贴块法培养VSMC,α-SM-actin染色鉴定。实验分为四组:对照组、γ-secretase抑制剂组(DAPT组)、PDGF-AA组和PDGFAA+γ-secretase抑制剂组(PDGF-AA+DAPT组)。实时荧光定量PCR(Real-time q PCR)检测Notch信号分子mRNA表达;Cell Titer96 Aqueous One Solution试剂盒检测细胞增殖活性;采用细胞划痕实验检测VSMC的迁移能力。结果腹主动脉VSMC表达Notch信号通路Jagged1、Jagged2、Notch1~3等几种主要的配体及受体;PDGF-AA刺激24h和48 h后分别导致Jagged2和Jagged1 mRNA表达显著增强(P0.01,n=4);与0 h相比,PDGF-AA刺激72 h后,Notch1、Notch3 mRNA表达显著增高(P0.01,n=4),而刺激24 h后Notch2 mRNA表达显著降低。PDGF-AA显著促进HES1(P0.05,n=4)、HEY2(P0.05,n=4)和转录因子Rbp-jКmRNA(P0.05,n=4)表达,DAPT抑制PDGF-AA介导的HES1、HEY2 mRNA表达增强(P0.01,n=4),但是进一步促进PDGF-AA诱导的Rbp-jКmRNA表达(P0.05,n=4);PDGF-AA刺激促进VSMC增殖(P0.01,n=5)和减少划痕余留面积(P0.01,n=4),两种效应均可被DAPT显著阻抑(P0.01,n=4)。结论 PDGF-AA调节了VSMC Notch信号分子表达,PDGF-AA部分通过激活Notch信号通路调节VSMC的增殖和迁移。

关 键 词:Notch  血管平滑肌细胞  血小板源生长因子AA  细胞增殖  细胞迁移
收稿时间:2015-07-03
修稿时间:2015-10-13

Notch Signaling Pathway Is Involved in Platelet Derived Growth Factor-AA Induced Vascular Smooth Muscle Cells Proliferation and Migration
WANG Jin-Xiang,ZHOU Fang,ZHU Guang-Xu,LIU Ju-Fen,ZHU Xiang-Qing,KANG Hua-Li,PANG Rong-Qing,HUANG Lan and PAN Xing-Hua. Notch Signaling Pathway Is Involved in Platelet Derived Growth Factor-AA Induced Vascular Smooth Muscle Cells Proliferation and Migration[J]. Chinese Journal of Arteriosclerosis, 2016, 24(9): 882-888
Authors:WANG Jin-Xiang  ZHOU Fang  ZHU Guang-Xu  LIU Ju-Fen  ZHU Xiang-Qing  KANG Hua-Li  PANG Rong-Qing  HUANG Lan  PAN Xing-Hua
Affiliation:Cell Biological Therapy Center of Kunming General Hospital, Chengdu Military Region of PLA & Cell Biological Medicine Integrated Engineering Laboratory of State and Region of Yunnan Province, Kunming, Yunnan 650032, China;Cell Biological Therapy Center of Kunming General Hospital, Chengdu Military Region of PLA & Cell Biological Medicine Integrated Engineering Laboratory of State and Region of Yunnan Province, Kunming, Yunnan 650032, China;Clinical College of Medicine,PLA Kunming General Hospital, Kunming Medical University, Kunming,Yunnan 650032, China;Cell Biological Therapy Center of Kunming General Hospital, Chengdu Military Region of PLA & Cell Biological Medicine Integrated Engineering Laboratory of State and Region of Yunnan Province, Kunming, Yunnan 650032, China;Cell Biological Therapy Center of Kunming General Hospital, Chengdu Military Region of PLA & Cell Biological Medicine Integrated Engineering Laboratory of State and Region of Yunnan Province, Kunming, Yunnan 650032, China;Cell Biological Therapy Center of Kunming General Hospital, Chengdu Military Region of PLA & Cell Biological Medicine Integrated Engineering Laboratory of State and Region of Yunnan Province, Kunming, Yunnan 650032, China;Cardiovascular Institute of Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China;Cell Biological Therapy Center of Kunming General Hospital, Chengdu Military Region of PLA & Cell Biological Medicine Integrated Engineering Laboratory of State and Region of Yunnan Province, Kunming, Yunnan 650032, China;Cardiovascular Institute of Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China;Cell Biological Therapy Center of Kunming General Hospital, Chengdu Military Region of PLA & Cell Biological Medicine Integrated Engineering Laboratory of State and Region of Yunnan Province, Kunming, Yunnan 650032, China
Abstract:
Keywords:Notch   Vascular Smooth Muscle Cell   Platelet Derived Growth Factor-AA   Cell Proliferation   Cell Migration
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