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

IF 2.4 4区生物学 Q4 CELL BIOLOGY

Biology of the Cell Pub Date : 2022-03-02 DOI:10.1111/boc.202100086

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

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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

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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。

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来源期刊

Biology of the Cell 生物-细胞生物学

CiteScore

5.30

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： The journal publishes original research articles and reviews on all aspects of cellular, molecular and structural biology, developmental biology, cell physiology and evolution. It will publish articles or reviews contributing to the understanding of the elementary biochemical and biophysical principles of live matter organization from the molecular, cellular and tissues scales and organisms. This includes contributions directed towards understanding biochemical and biophysical mechanisms, structure-function relationships with respect to basic cell and tissue functions, development, development/evolution relationship, morphogenesis, stem cell biology, cell biology of disease, plant cell biology, as well as contributions directed toward understanding integrated processes at the organelles, cell and tissue levels. Contributions using approaches such as high resolution imaging, live imaging, quantitative cell biology and integrated biology; as well as those using innovative genetic and epigenetic technologies, ex-vivo tissue engineering, cellular, tissue and integrated functional analysis, and quantitative biology and modeling to demonstrate original biological principles are encouraged.