hnRNPA2/B1 Ameliorates LPS-Induced Endothelial Injury through NF-κB Pathway and VE-Cadherin/β-Catenin Signaling Modulation In Vitro
hnRNPA2/B1 Ameliorates LPS-Induced Endothelial Injury through NF-κB Pathway and VE-Cadherin/β-Catenin Signaling Modulation In Vitro
复制标题
hnRNPA2/B1 通过 NF-kappa B 通路和 VE-Cadherin/beta-Catenin 信号传导调节体外改善 LPS 诱导的内皮损伤
DOI：
10.1155/2020/6458791
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发表时间：
2020-05-30
影响因子：
4.6
通讯作者：
Yu, Weifeng
中科院分区：
文献类型：
--
作者：
Chen, Yi;Tang, Dan;Yu, Weifeng
异质核核糖核蛋白A2/B1（hnRNPA 2/B1）是一种参与调节RNA加工、细胞代谢、迁移、增殖和凋亡的蛋白质。然而，hnRNPA 2/B1对损伤的内皮细胞（EC）的作用仍不清楚。我们研究了hnRNPA 2/B1对脂多糖（LPS）诱导的人脐静脉内皮细胞（HUVECs）血管内皮损伤的影响及其机制。用LPS诱导EC损伤，通过检测hnRNPA 2/B1抑制和过表达后EC通透性和炎症因子表达，观察hnRNPA 2/B1在EC屏障功能障碍和炎症反应中的作用。为了探讨hnRNPA 2/B1调节内皮损伤的潜在机制，我们研究了内皮细胞中VE-钙粘蛋白/β-连环蛋白通路和NF-κ B活化。结果显示，LPS刺激HUVECs后hnRNPA 2/B1表达增加。此外，敲低hnRNPA 2/B1通过增加EC渗透性和促进炎性细胞因子TNF-α、IL-1 β和IL-6的分泌而加重内皮损伤。hnRNPA 2/B1的过表达可降低LPS刺激的HUVEC的通透性和炎症反应，同时增加VE-Cadherin和beta-catenin的表达。此外，hnRNPA 2/B1的抑制增加了LPS诱导的NF-κ B活化，并减少了VE-钙粘蛋白/β-连环蛋白通路。综上所述，这些结果表明hnRNPA 2/B1可以通过调节NF-κ B和VE-钙粘蛋白/β-连环蛋白通路来调节LPS诱导的EC损伤。
Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) is a protein involved in the regulation of RNA processing, cell metabolism, migration, proliferation, and apoptosis. However, the effect of hnRNPA2/B1 on injured endothelial cells (ECs) remains unclear. We investigated the effect of hnRNPA2/B1 on lipopolysaccharide- (LPS-) induced vascular endothelial injury in human umbilical vein endothelial cells (HUVECs) and the underlying mechanisms. LPS was used to induce EC injury, and the roles of hnRNPA2/B1 in EC barrier dysfunction and inflammatory responses were measured by testing endothelial permeability and the expression of inflammatory factors after the suppression and overexpression of hnRNPA2/B1. To explore the underlying mechanism by which hnRNPA2/B1 regulates endothelial injury, we studied the VE-cadherin/beta-catenin pathway and NF-kappa B activation in HUVECs. The results showed that hnRNPA2/B1 was elevated in LPS-stimulated HUVECs. Moreover, knockdown of hnRNPA2/B1 aggravated endothelial injury by increasing EC permeability and promoting the secretion of the inflammatory cytokines TNF-alpha, IL-1 beta, and IL-6. Overexpression of hnRNPA2/B1 can reduce the permeability and inflammatory response of HUVEC stimulated by LPS in vitro, while increasing the expression of VE-Cadherin and beta-catenin. Furthermore, the suppression of hnRNPA2/B1 increased the LPS-induced NF-kappa B activation and reduced the VE-cadherin/beta-catenin pathway. Taken together, these results suggest that hnRNPA2/B1 can regulate LPS-induced EC damage through regulating the NF-kappa B and VE-cadherin/beta-catenin pathways.