Lipopolysaccharide increases exosomes secretion from endothelial progenitor cells by toll-like receptor 4 dependent mechanism

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Applied Bio Materials Pub Date : 2022-03-02 DOI:10.1111/boc.202100086

Liang Xia, Xiaotian Wang, Weidong Yao, Meihui Wang, Junhui Zhu

{"title":"Lipopolysaccharide increases exosomes secretion from endothelial progenitor cells by toll-like receptor 4 dependent mechanism","authors":"Liang Xia, Xiaotian Wang, Weidong Yao, Meihui Wang, Junhui Zhu","doi":"10.1111/boc.202100086","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background Information</h3>\n \n <p>Endothelial progenitor cells (EPCs) can exert angiogenic effects by a paracrine mechanism, where exosomes work as an important mediator. Recent studies reported functional expression of toll-like receptor (TLR) 4 on human EPCs and dose-dependent effects of lipopolysaccharide (LPS) on EPC angiogenic properties. To study the effects of TLR4/LPS signaling on EPC-derived exosomes (Exo) and clarify the mechanism, we investigated the role of LPS on exosomes secretion from human EPCs and tested their anti-oxidation/senescence functions. We employed the inhibitors of the plasma membrane Ca<sup>2+</sup>-ATPase (PMCA), endoplasmic reticulum Ca<sup>2+</sup>-ATPase (ERCA), PLC-IP<sub>3</sub> pathway and store-operated calcium entry to assess the effects of LPS on EPC intracellular calcium signalings which critical for exosome secretion.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>LPS induced the release of Exo in a TLR4-dependent manner in vitro, which effect can be partly abrogated by an membrane-permeable IP <sub>3</sub> R antagonist, 2-aminoethyl diphenylborinate (2-APB), but not PLC inhibitor, U-73122. The LPS can significantly delay the fallback of [Ca<sup>2+</sup>]i after isolating the cellular PMCA activity, and disturb PMCA 1/4 expression. The distribution of elevated intracellular calcium seemed coincident with the development of the multivesicular bodies (MVBs). furthermore, the anti-oxidation/senescence properties of LPS-induced Exo were validated by the senescence-associated β-galactosidase activity assay and reactive oxygen species (ROS) related H<sub>2</sub>DCF-DA assay.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>The mechanism of PMCA downregulation and IP<sub>3</sub>R-dependent ER Ca<sup>2+</sup> release may contribute to the pro-exosomal effects of LPS on EPCs.</p>\n </section>\n \n <section>\n \n <h3> Significance</h3>\n \n <p>This study provides new insights into the potential role of LPS/TLR4 pathway in regulating EPC-derived exosomes, which may help to develop some feasible approach to manipulate the Exo secretion and promote the clinical application of EPCs therapy in future.</p>\n </section>\n </div>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2022-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Bio Materials","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/boc.202100086","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}

引用次数: 2

Abstract

Background Information

Endothelial progenitor cells (EPCs) can exert angiogenic effects by a paracrine mechanism, where exosomes work as an important mediator. Recent studies reported functional expression of toll-like receptor (TLR) 4 on human EPCs and dose-dependent effects of lipopolysaccharide (LPS) on EPC angiogenic properties. To study the effects of TLR4/LPS signaling on EPC-derived exosomes (Exo) and clarify the mechanism, we investigated the role of LPS on exosomes secretion from human EPCs and tested their anti-oxidation/senescence functions. We employed the inhibitors of the plasma membrane Ca²⁺-ATPase (PMCA), endoplasmic reticulum Ca²⁺-ATPase (ERCA), PLC-IP₃ pathway and store-operated calcium entry to assess the effects of LPS on EPC intracellular calcium signalings which critical for exosome secretion.

Results

LPS induced the release of Exo in a TLR4-dependent manner in vitro, which effect can be partly abrogated by an membrane-permeable IP ₃ R antagonist, 2-aminoethyl diphenylborinate (2-APB), but not PLC inhibitor, U-73122. The LPS can significantly delay the fallback of [Ca²⁺]i after isolating the cellular PMCA activity, and disturb PMCA 1/4 expression. The distribution of elevated intracellular calcium seemed coincident with the development of the multivesicular bodies (MVBs). furthermore, the anti-oxidation/senescence properties of LPS-induced Exo were validated by the senescence-associated β-galactosidase activity assay and reactive oxygen species (ROS) related H₂DCF-DA assay.

Conclusions

The mechanism of PMCA downregulation and IP₃R-dependent ER Ca²⁺ release may contribute to the pro-exosomal effects of LPS on EPCs.

Significance

This study provides new insights into the potential role of LPS/TLR4 pathway in regulating EPC-derived exosomes, which may help to develop some feasible approach to manipulate the Exo secretion and promote the clinical application of EPCs therapy in future.

Abstract Image

查看原文本刊更多论文

脂多糖通过toll样受体4依赖性机制增加内皮祖细胞外泌体的分泌

内皮祖细胞（EPCs）可以通过旁分泌机制发挥血管生成作用，其中外泌体是一种重要的介质。最近的研究报道了toll样受体（TLR）4在人EPC上的功能性表达以及脂多糖（LPS）对EPC血管生成特性的剂量依赖性影响。为了研究TLR4/LPS信号对EPC衍生的外泌体（Exo）的影响并阐明其机制，我们研究了LPS对人EPC外泌体分泌的作用，并测试了其抗氧化/衰老功能。我们使用质膜Ca2+-ATPase（PMCA）、内质网Ca2+-ATP酶（ERCA）、PLC‐IP3通路和储存操作的钙进入抑制剂来评估LPS对EPC细胞内钙信号的影响，这对外泌体分泌至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464