Regulatory and functional mechanism of angiopoietin-like protein-4 in gastric epithelial cells with <italic style="font-style: italic">Helicobacter pylori</italic> infection

Wanyan CHEN; Gengyu YUE; Xiaolin XU; Yuan ZHUANG

doi:10.16016/j.2097-0927.202309118

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Regulatory and functional mechanism of angiopoietin-like protein-4 in gastric epithelial cells with Helicobacter pylori infection

Basic Medicine | 更新时间：2026-01-09

- Regulatory and functional mechanism of angiopoietin-like protein-4 in gastric epithelial cells with Helicobacter pylori infection
- Journal of Army Medical University Vol. 46, Issue 9, Pages: 997-1006(2024)
- 作者机构：
  
  1.400038 重庆，陆军军医大学(第三军医大学)药学与检验医学系微生物与生化药学教研室
  2.563000 贵州遵义，遵义医科大学附属医院消化内科
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(82070578)
- DOI：10.16016/j.2097-0927.202309118
  CLC： R322.44;R378.99;R341
- Received：21 September 2023，
  
  Revised：2023-12-27，
  
  Published：15 May 2024
- 稿件说明：
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Wanyan CHEN, Gengyu YUE, Xiaolin XU, et al. Regulatory and functional mechanism of angiopoietin-like protein-4 in gastric epithelial cells with Helicobacter pylori infection[J]. Journal of Army Medical University, 2024, 46(9): 997-1006.
DOI：

Wanyan CHEN, Gengyu YUE, Xiaolin XU, et al. Regulatory and functional mechanism of angiopoietin-like protein-4 in gastric epithelial cells with Helicobacter pylori infection[J]. Journal of Army Medical University, 2024, 46(9): 997-1006. DOI： 10.16016/j.2097-0927.202309118.

摘要

目的

探究血管生成素样蛋白4(angiopoietin-like 4

ANGPTL4)在幽门螺杆菌(

Helicobacter pylori

，

H.pylori

)感染的胃上皮细胞中的表达调控及其功能机制。

方法

收集2021年11月陆军军医大学第二附属医院消化内科胃镜室

H.pylori

阳性患者的胃镜标本以及

H.pylori

感染小鼠的胃组织，利用免疫荧光染色技术检测ANGPTL4在胃组织中的表达部位；用

H.pylori

感染胃上皮细胞和胃类器官，运用实时荧光定量PCR和Western blot等检测ANGPTL4的表达；探讨

H.pylori

感染诱导ANGPTL4表达的调控机制；利用ANGPTL4重组蛋白刺激胃上皮细胞，检测其对密封蛋白1 (claudin 1，CLDN1)表达的影响。

结果

H.pylori

感染能显著诱导胃上皮细胞ANGPTL4表达增加，且具有毒力因子CagA依赖性、细菌浓度依赖性和感染时间依赖性(

＜0.05)；相对于未感染组和CagA敲除(△

cagA

)

H.pylori

感染组，野生型(wild-type，WT)

H.pylori

感染组的人和小鼠胃类器官ANGPTL4表达显著上调(

＜0.05)；调控机制方面，阻断信号通路NF-κB可明显抑制胃上皮细胞ANGPTL4表达增加(

＜0.05)；功能机制方面，ANGPTL4重组蛋白通过激活通路ERK下调胃上皮细胞CLDN1表达(

＜0.05)。

结论

H.pylori

依赖毒力因子CagA通过激活NF-κB信号通路诱导胃上皮细胞表达ANGPTL4；AN

GPTL4激活通路ERK下调胃上皮细胞CLDN1表达，从而影响

H.pylori

感染相关胃部疾病的发展。

Abstract

Objective

To explore the regulatory and functional mechanism of angiopoietin-like 4 (ANGPTL4) expression in gastric epithelial cells infected with

Helicobacter pylori

(

H.pylori

Methods

H.pylori

-positive gastric specimens from Department of Gastroenterology of second Affiliated Hospital of Army Medical University in November 2021 and the gastric tissues of

H.pylori

-infected mice were collected

and the expression locations of ANGPTL4 in these gastric tissues were detected by immunofluorescence assay. After gastric epithelial cells and gastric organoids were infected with

H.pylori

the expression of ANGPTL4 was detected by real-time PCR and Western blotting. The regulatory mechanism of

H.pylori

-induced ANGPTL4 expression was investigated by cellular models above. Recombinant ANGPTL4 was used to stimulate gastric epithelial cells to investigate the effect of ANGPTL4 on the claudin 1 (CLDN1) expression.

Results

H.pylori

infection significantly increased the expression of ANGPTL4 in gastric epithelial cells in a CagA-dependent

bacterial concentration-dependent and infection time-dependent manner (

0.05). Compared to uninfected cells and CagA knockout (△cagA)

H.pylori

-induced ones

the ANGPTL4 expression was significantly increased in WT

H.pylori

-infected human and mouse gastric organoid (

0.05). Blocking NF-κB signaling pathway significantly inhibited the enhanced ANGPTL4 expression in

H.pylori

-infected gastric epithelial cells (

0.05). Recombinant ANGPTL4 activated ERK signaling pathway to down-regulate the CLDN1 expression in gastric epith

elial cells (

0.05).

Conclusion

H.pylori

activates NF-κB signaling pathway to up-regulate ANGPTL4 expression in gastric epithelial cells in a CagA-dependent manner

and ANGPTL4 activates ERK signaling pathway to down-regulate the CLDN1 expression in gastric epithelial cells

which may contributes to the development of gastric diseases induced by

H.pylori

infection.

关键词

Keywords

references

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Regulatory and functional mechanism of angiopoietin-like protein-4 in gastric epithelial cells with Helicobacter pylori infection

DOI：10.16016/j.2097-0927.202309118

摘要

Abstract

关键词

Keywords

references