Role of SHP-1 in angiotensin- (1-7) antagonizing angiotensin Ⅱ-induced connexin remodeling in mouse HL-1 cardiomyocytes

Yihao LIU; Li LU; Li CAO; Yunlin CHEN; Yaowen WANG; Jinqi FAN; Yuehui YIN

doi:10.16016/j.1000-5404.201801240

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Role of SHP-1 in angiotensin- (1-7) antagonizing angiotensin Ⅱ-induced connexin remodeling in mouse HL-1 cardiomyocytes

Basic Medicine | 更新时间：2026-01-09

- Role of SHP-1 in angiotensin- (1-7) antagonizing angiotensin Ⅱ-induced connexin remodeling in mouse HL-1 cardiomyocytes
- Journal of Third Military Medical University Vol. 40, Issue 13, Pages: 1179-1184(2018)
- 作者机构：
  
  400010 重庆，重庆医科大学附属第二医院心血管内科
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81570302);the National Natural Science Foundation for Young Scholars of China(81500250)
- DOI：10.16016/j.1000-5404.201801240
  CLC： R322.11;R329-33;R329.28
- Received：25 January 2018，
  
  Revised：2018-04-03，
  
  Published：15 July 2018
- 稿件说明：
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Yihao LIU, Li LU, Li CAO, et al. Role of SHP-1 in angiotensin- (1-7) antagonizing angiotensin Ⅱ-induced connexin remodeling in mouse HL-1 cardiomyocytes[J]. Journal of Third Military Medical University, 2018, 40(13): 1179-1184.
DOI：

Yihao LIU, Li LU, Li CAO, et al. Role of SHP-1 in angiotensin- (1-7) antagonizing angiotensin Ⅱ-induced connexin remodeling in mouse HL-1 cardiomyocytes[J]. Journal of Third Military Medical University, 2018, 40(13): 1179-1184. DOI： 10.16016/j.1000-5404.201801240.

摘要

目的

探讨血管紧张素1-7[angiotensin 1-7，Ang-(1-7)]是否通过SHP-1来抑制血管紧张素Ⅱ(angiotensin Ⅱ，AngⅡ)诱导的c-Src激活，从而改善缝隙连接蛋白43(connexin 43，Cx43)的表达以及功能。

方法

以小鼠心房肌细胞系(HL-1细胞系)作为研究对象，分为Control组、AngⅡ组、AngⅡ+SU6656(c-Src抑制剂)组、AngⅡ+Ang-(1-7)组、AngⅡ+Ang-(1-7)+SSG (SHP-1抑制剂)组，Western blot分别检测p-c-Src、Cx43、SHP-1的表达，细胞免疫荧光、划痕标记染料示踪技术观察Cx43空间分布以及缝隙连接功能。

结果

与Control组比较，高浓度AngⅡ(10

-6

mol/L)干预后p-c-Src表达增加(

＜0.01)，Cx43表达降低(

＜0.05)，Cx43传导距离缩短；SU6656和Ang-(1-7)预处理可抑制AngⅡ诱导的c-Src激活，Cx43表达增加(

＜0.05)，Cx43传导距离增加；同时Ang-(1-7)预处理明显地促进SHP-1的表达增加(

＜0.05)。与AngⅡ+Ang-(1-7)组比较，AngⅡ+Ang-(1-7)+SSG组SHP-1表达降低(

＜0.05)，p-c-Src表达增加(

＜0.01)，细胞Cx43表达降低(

＜0.05)，Cx43传导距离缩短。

结论

Ang-(1-7)通过增加SHP-1表达从而抑制c-Src活性，进而发挥对AngⅡ的拮抗作用，使Cx43表达上升并改善缝隙连接功能。

Abstract

Objective

To investigate whether angiotensin 1-7 [Ang-(1-7)] inhibits angiotensin Ⅱ (AngⅡ)-induced c-Src activation through SHP-1

and thereby improves Cx43 expression and function.

Methods

Mouse HL-1 cardiomyocytes were treated respectively by AngⅡ

AngⅡ+SU6656 (a specific c-Src inhibitor)

AngⅡ+Ang-(1-7)

and AngⅡ+Ang-(1-7)+SSG (a specific SHP-1 inhibitor)

and those without any treatment served as control cells. Western blotting was used to detect the expression levels of p-c-Src

Cx43 and SHP-1 in these cells. Cell immunofluorescence staining and scrape-loading and dye transfer (SLDT) tracing were employed to observe the spatial distribution of Cx43 and the function of gap junctions.

Results

Compared with the control cells

higher concentration of AngⅡ (10-6 mol/L) treatment increased the expression of p-c-Src (

0.01)

but inhibited the expression of Cx43 (

0.05) and shortened the conduction distance of gap junction. While

Ang-(1-7)+SU6656 pretreatment inhibited the activation of c-Src induced by AngⅡ (

0.05)

enhanced the expression of Cx43 and shorten the conduction distance of gap junction. At the same time

Ang-(1-7) precondition effectively enhanced the expression of SHP-1 (

0.05). Compared with the AngⅡ+Ang-(1

-7) treated cells

AngⅡ+Ang-(1-7)+SSG significantly inhibited SHP-1 expression (

0.05)

increased that of p-c-Src (

0.01) and decreased Cx43 expression (

0.05).

Conclusion

Ang-(1-7) inhibits c-Src activity by increasing the expression of SHP-1

thereby exerts an antagonistic effect on AngⅡ

and then results in the up-regulation of Cx43 and improvement of gap junction function.

关键词

Keywords

references

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