Experimental study on the mechanism of transgelin regulating the formation of abdominal aortic aneurysm

WANG Bei-ming; FENG Zeng-li; LIU Yan; JIA Kai-ning; ZHANG Shou-yong; WANG Hai-gang

doi:10.11659/jjssx.10E022089

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Experimental study on the mechanism of transgelin regulating the formation of abdominal aortic aneurysm

Basic Research | 更新时间：2023-11-24

- Experimental study on the mechanism of transgelin regulating the formation of abdominal aortic aneurysm
- JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY Vol. 32, Issue 11, Pages: 968-973(2023)
- 作者机构：
  
  华北石油管理局总医院药剂科，河北任丘 062552
- 作者简介：
- 基金信息：
- DOI：10.11659/jjssx.10E022089
  CLC： R543.16
- Published：25 November 2023，
  
  Received：18 October 2022，
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王蓓明,冯增利,刘艳等.转胶蛋白调控腹主动脉瘤形成机制的实验研究[J].局解手术学杂志,2023,32(11):968-973.

WANG Bei-ming,FENG Zeng-li,LIU Yan,et al.Experimental study on the mechanism of transgelin regulating the formation of abdominal aortic aneurysm[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2023,32(11):968-973.
王蓓明,冯增利,刘艳等.转胶蛋白调控腹主动脉瘤形成机制的实验研究[J].局解手术学杂志,2023,32(11):968-973. DOI： 10.11659/jjssx.10E022089.

WANG Bei-ming,FENG Zeng-li,LIU Yan,et al.Experimental study on the mechanism of transgelin regulating the formation of abdominal aortic aneurysm[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2023,32(11):968-973. DOI： 10.11659/jjssx.10E022089.

摘要

目的

探讨转胶蛋白（TAGLN）对腹主动脉瘤（AAA）的影响及其作用机制。

方法

通过血管紧张素Ⅱ（AngⅡ）诱导AAA小鼠模型，20只ApoE-/-小鼠建模当天于主动脉外膜下分别注射40 μL 对照慢病毒（NC-LV）和40 μL TAGLN过表达慢病毒（TAGLN-LV），作为AAA+NC-LV组和AAA+TAGLN-LV组，每组10只；10只ApoE-/-小鼠泵入等体积的生理盐水并注射40 μL NC-LV，作为NC-LV组。将血管平滑肌细胞（VSMC）分为Control组（不进行转染）、NC-siRNA组（转染NC-siRNA）、TAGLN-siRNA组（转染TAGLN-siRNA）、NC-OE组（转染NC-LV）和TAGLN-OE组（转染TAGLN-LV）。通过HE染色观察小鼠主动脉组织病变。采用CCK-8分析细胞增殖能力，Transwell法分析VSMC的迁移能力。qRT-PCR及Western blot检测TAGLN、α-平滑肌肌动蛋白（α-SMA）、骨桥蛋白（OPN）、核因子-κB（NF-κB） p65、p-NF-κB p65和MMP-9的表达。

结果

与AAA+NC-LV组相比，AAA+TAGLN-LV组的TAGLN mRNA和蛋白表达水平均升高（

0.05）；腹主动脉形态基本恢复正常，AAA特征明显减少，α-SMA蛋白表达水平升高（

0.05），而OPN、p-NF-κB p65/NF-κB p65和MMP-9降低（

0.05）。与Control组相比，TAGLN-siRNA组的TAGLN mRNA和蛋白表达水平降低（

0.05），相对细胞活力和迁移细胞数升高/增加（

0.05），α-SMA蛋白表达水平降低（

0.05），OPN、p-NF-κB p65/NF-κB p65和MMP-9升高（

0.05），而TAGLN-OE组以上指标变化与TAGLN-siRNA组相反（

0.05）。

结论

上调TAGLN可有效抑制AAA的发生发展，其机制可能与TAGLN对VSMC的表型转换和NF-κB/MMP-9信号通路的调控有关。

Abstract

Objective

To investigate the effect of transgelin （TAGLN） on abdominal aortic aneurysm （AAA） and its mechanism.

Methods

The AAA mice model was induced by angiotensin Ⅱ （Ang Ⅱ）， and 20 ApoE-/- mice were injected with 40 μL of negative control lentivirus （NC-LV） and 40 μL of TAGLN overexpressed lentivirus （TAGLN-LV） under the adventitia of aorta on the day of modeling as the AAA+NC-LV group and the AAA+TAGLN-LV group， with 10 mice in each group； other 10 ApoE-/- mice were pumped with the same volume of saline and injected with 40 μL of NC-LV as the NC-LV group. The vascular smooth muscle cells （VSMC） were divided into the Control group （without transfection）， NC-siRNA group （transfected with NC-siRNA）， TAGLN-siRNA group （transfected with TAGLN-siRNA）， NC-OE group （transfected with NC-LV） and TAGLN-OE group （transfected with TAGLN-LV）. The pathological changes of mouse aorta tissue were observed by HE staining. The ability of cell proliferation was analyzed by CCK-8 and the migration ability of VSMC was analyzed by Transwell method. The expressions of TAGLN， α-smooth muscle actin （α-SMA）， osteopontin （OPN）， nuclear factor-kappa B（NF-κB） p65， p-NF-κB p65 and MMP-9 were detected by qRT-PCR and Western blot.

Results

Compared with the AAA+NC-LV group， the expression levels of TAGLN mRNA and protein in the AAA+TAGLN-LV group both increased （

0.05）， the morphology of abdominal aorta was basically returned to normal， the characteristics of AAA decreased， the expression level of α-SMA protein increased （

0.05）， while OPN， p-NF-κB p65/NF-κB p65 and MMP-9 decreased （

0.05）. Compared with the Control group， the expression levels of TAGLN mRNA and protein in the TAGLN-siRNA group decreased （

0.05）， the relative cell viability and the number of migration cells increased （

0.05）， the expression level of α-SMA protein decreased （

0.05）， OPN， p-NF-κB p65/NF-κB p65 and MMP-9 increased in the TAGLN-siRNA group （

0.05）， while the changes of the obove indexes in the TAGLN-OE group were opposite to those in the TAGLN-siRNA group（

0.05）.

Conclusion

Up-regulation of TAGLN can effectively inhibit the occurrence and development of AAA， and its mechanism may be related to the regulation of TAGLN on the phenotypic conversion of VSMC and NF-κB/MMP-9 signaling pathway.

关键词

腹主动脉瘤转胶蛋白血管平滑肌细胞表型转换核因子-κB基质金属蛋白酶-9

Keywords

abdominal aortic aneurysmtransgelinvascular smooth muscle cellsphenotypic conversionnuclear factor-κBmatrix metalloproteinase-9

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