HnRNPA2/B1 Ameliorates LPS-Induced Endothelial Injury through NF-κB Pathway and VE-Cadherin/β-Catenin Signaling Modulation In Vitro.

Yi Chen,Hexin Yan,Tianjie Yuan,Linjie Zhu,Weifeng Yu,Dan Tang,Yingfu Jiao

doi:10.1155/2020/6458791

Abstract

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/β-catenin pathway and NF-κB 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-α, IL-1β, 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 β-catenin. Furthermore, the suppression of hnRNPA2/B1 increased the LPS-induced NF-κB activation and reduced the VE-cadherin/β-catenin pathway. Taken together, these results suggest that hnRNPA2/B1 can regulate LPS-induced EC damage through regulating the NF-κB and VE-cadherin/β-catenin pathways.

Highlights

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection [1]
To explore the action underlying the effects of hnRNPA2/B1 on endothelial permeability, we further evaluated the expression of adhesion junction proteins in LPS-treated human umbilical vein endothelial cells (HUVECs)
The upregulation of hnRNPA2/B1 may reverse LPS-induced endothelial barrier damage effect. These results suggest that hnRNPA2/B1 has a protective effect on endothelial permeability changes in HUVECs induced by LPS

Summary

Introduction

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection [1]. The most severe clinical manifestation of sepsis, is often accompanied by severe hypotension, microvascular perfusion insufficiency, and tissue damage, leading to multiple organ dysfunctions [2,3,4]. The vascular barrier is mainly composed of endothelial cells (ECs), cell-cell intercellular junctions, and extracellular components. The endothelial barrier is in a semipermeable state, and substances in the blood can be transferred to peripheral tissues. EC integrity is necessary to maintain vascular homeostasis and tissue fluid balance. EC injury triggered by the inflammatory response may lead to increased vascular permeability, protein leakage, inflammatory cell infiltration, uncontrollable tissue edema, and microthrombosis [7,8,9]

Methods

Findings

Discussion

Conclusion