血管生成素样蛋白8促进大鼠主动脉血管平滑肌细胞表型转化

doi:10.16352/j.issn.1001-6325.2022.05.009

基础医学与临床 ›› 2022, Vol. 42 ›› Issue (5): 745-751.doi: 10.16352/j.issn.1001-6325.2022.05.009

血管生成素样蛋白8促进大鼠主动脉血管平滑肌细胞表型转化

孙秋菊, 焦晓璐, 于华惠, 李凡, 吕倩雯, 王钰, 秦彦文^*

首都医科大学附属北京安贞医院北京市心肺血管疾病研究所, 北京 100029

收稿日期:2022-02-17 修回日期:2022-03-22 出版日期:2022-05-05 发布日期:2022-04-28
通讯作者: * qinyanwen@126.com
基金资助:
国家自然科学基金(81970224)

Angiopoietin-like protein 8 promotes phenotypic transformation of rat aorta vascular smooth muscle cells

SUN Qiu-ju, JIAO Xiao-lu, YU Hua-hui, LI Fan, LYU Qian-wen, WANG Yu, QIN Yan-wen^*

Beijing Anzhen Hospital,Capital Medical University,Beijing Institute of Heart,Lung and Blood Vessel Diseases,Beijing 100029,China

Received:2022-02-17 Revised:2022-03-22 Online:2022-05-05 Published:2022-04-28
Contact: * qinyanwen@126.com

摘要/Abstract

摘要： 目的探讨血管生成素样蛋白8(ANGPTL8)对大鼠主动脉血管平滑肌细胞(VSMCs)表型转化的作用机制。方法 ApoE^-/-小鼠西方饮食12周构建动脉粥样硬化模型小鼠。免疫荧光染色检测ANGPTL8在动脉硬化斑块中的表达与定位;采用慢病毒转染VSMCs构建 ANGPTL8过表达稳转细胞株;将细胞随机分为5组,对照(control)组、ANGPTL8过表达(LV-ANGPTL8)组、ox-LDL(50 mg/L)组、(ox-LDL+ ANGPTL8过表达)组、[ANGPTL8过表达+ERK通路抑制剂(PD98059)]组。划痕实验观察细胞迁移; Western blot检测VSMCs 中α-SMA、SM22α、OPN、PCNA、Ki67的蛋白表达。结果过表达ANGPTL8后促进了VSMCs中OPN、PCNA、Ki67的蛋白表达(P＜0.05),抑制了α-SMA、SM22α的蛋白表达(P＜0.05),促进了VSMCs的迁移能力(P＜0.05);加入ERK通路抑制剂PD98059后OPN、PCNA、Ki67的蛋白表达减少(P＜0.05),α-SMA、SM22α的蛋白表达增加(P＜0.05),VSMCs的迁移能力降低(P＜0.05)。结论 ANGPTL8可能通过激活ERK通路促进VSMCs的表型转化。

关键词: 血管生成素样蛋白8(ANGPTL8), ERK通路, 平滑肌细胞

Abstract: Objective To explore the role and mechanism of angiopoietin-like protein 8 (ANGPTL8) on phenotypic transformation of rat aorta vascular smooth muscle cells (VSMCs). Methods ApoE^-/- male mice (8 weeks of age) were fed with a western diet for 12 weeks to build the atherosclerosis mouse model. The expression and localization of ANGPTL8 in atherosclerotic plaques were detected by immunofluorescence staining. Stable transfections of the ANGPTL8 over-expression vector were performed. VSMCs were randomly divided into 5 groups: control group,LV-ANGPTL8 group,ox-LDL (50 mg/L)group,(ox-LDL+LV-ANGPTL8) group and (LV-ANGPTL8+PD98059 group. And cell migration was observed by wound-healing assay. The protein expressions of α-SMA, SM22α, OPN, PCNA and Ki67 in VSMCs was detected by Western blot. Results ANGPTL8 over-expression promoted the expression of OPN, PCNA and Ki67 in VSMCs (P＜0.05), decreased the expression of α-SMA and SM22α(P＜0.05) and enhanced migration ability of VSMCs(P＜0.05). After adding ERK pathway inhibitor PD98059, the expression of OPN, PCNA and Ki67 decreased (P＜0.05), α-SMA and SM22α expression increased(P＜0.05), and the migration capability of the VSMCs decreased (P＜0.05). Conclusions ANGPTL8 maybe promotes phenotypic transformation of VSMCs by activating ERK pathway.

Key words: angiopoietin-like protein 8(ANGPTL8), ERK pathway, vascular smooth muscle cells

中图分类号:

R363.1

孙秋菊, 焦晓璐, 于华惠, 李凡, 吕倩雯, 王钰, 秦彦文. 血管生成素样蛋白8促进大鼠主动脉血管平滑肌细胞表型转化[J]. 基础医学与临床, 2022, 42(5): 745-751.

SUN Qiu-ju, JIAO Xiao-lu, YU Hua-hui, LI Fan, LYU Qian-wen, WANG Yu, QIN Yan-wen. Angiopoietin-like protein 8 promotes phenotypic transformation of rat aorta vascular smooth muscle cells[J]. Basic & Clinical Medicine, 2022, 42(5): 745-751.

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血管生成素样蛋白8促进大鼠主动脉血管平滑肌细胞表型转化

Angiopoietin-like protein 8 promotes phenotypic transformation of rat aorta vascular smooth muscle cells

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