Dataset Information

Endothelial Cell Morphology Regulates Inflammatory Cells Through MicroRNA Transferred by Extracellular Vesicles.

ABSTRACT: Vascular inflammation plays an important role in the pathogenesis and the development of cardiovascular diseases such as arteriosclerosis and restenosis, and the dysfunction of endothelial cells (ECs) may result in the activation of monocytes and other inflammatory cells. ECs exhibit an elongated morphology in the straight part of arteries but a cobblestone shape near the pro-atherogenic region such as branch bifurcation. Although the effects of hemodynamic forces on ECs have been widely studied, it is not clear whether the EC morphology affects its own function and thus the inflammatory response of monocytes. Here we showed that elongated ECs cultured on poly-(dimethyl siloxane) membrane surface with microgrooves significantly suppressed the activation of the monocytes in co-culture, in comparison to ECs with a cobblestone shape. The transfer of EC-conditioned medium to monocytes had the same effect, suggesting that soluble factors were involved in EC-monocyte communication. Further investigation demonstrated that elongated ECs upregulated the expression of anti-inflammatory microRNAs, especially miR-10a. Moreover, miR-10a was found in the extracellular vesicles (EVs) released by ECs and transferred to monocytes, and the inhibition of EV secretion from ECs repressed the upregulation of miR-10a. Consistently, the inhibition of miR-10a expression in ECs reduced their anti-inflammatory effect on monocytes. These results reveal that the EC morphology can regulate inflammatory response through EVs, which provides a basis for the design and the optimization of biomaterials for vascular tissue engineering.

SUBMITTER: Liang J

PROVIDER: S-EPMC7248333 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Endothelial Cell Morphology Regulates Inflammatory Cells Through MicroRNA Transferred by Extracellular Vesicles.

Liang Jiaqi J Gu Shuangying S Mao Xiuli X Tan Yiling Y Wang Huanli H Li Song S Zhou Yue Y

Frontiers in bioengineering and biotechnology 20200519

Vascular inflammation plays an important role in the pathogenesis and the development of cardiovascular diseases such as arteriosclerosis and restenosis, and the dysfunction of endothelial cells (ECs) may result in the activation of monocytes and other inflammatory cells. ECs exhibit an elongated morphology in the straight part of arteries but a cobblestone shape near the pro-atherogenic region such as branch bifurcation. Although the effects of hemodynamic forces on ECs have been widely studied ...[more]

PMID: 32509739

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Project description:Extracellular vesicles (EV) mediated intercellular communication between monocytes and endothelial cells (EC) might play a major role in vascular inflammation and atherosclerotic plaque formation during cardiovascular diseases (CVD). While critical involvement of small (exosomes) and large EV (microvesicles) in CVD has recently been appreciated, the pro- and/or anti-inflammatory impact of a bulk EV (exosomes?+?microvesicles) on vascular cell function as well as their inflammatory capacity are poorly defined. This study aims to unravel the immunomodulatory content of EV bulk derived from control (uEV) and TNF-? induced inflamed endothelial cells (tEV) and to define their capacity to affect the inflammatory status of recipients monocytes (THP-1) and endothelial cells (HUVEC) in vitro. Here, we show that EV derived from inflamed vascular EC were readily taken up by THP-1 and HUVEC. Human inflammation antibody array together with ELISA revealed that tEV contain a pro-inflammatory profile with chemotactic mediators, including intercellular adhesion molecule (ICAM)-1, CCL-2, IL-6, IL-8, CXCL-10, CCL-5, and TNF-? as compared to uEV. In addition, EV may mediate a selective transfer of functional inflammatory mediators to their target cells and modulate them toward either pro-inflammatory (HUVEC) or anti/pro-inflammatory (THP-1) mode. Accordingly, the expression of pro-inflammatory markers (IL-6, IL-8, and ICAM-1) in tEV-treated HUVEC was increased. In the case of THP-1, EC-EV do induce a mixed of pro- and anti-inflammatory response as indicated by the elevated expression of ICAM-1, CCL-4, CCL-5, and CXCL-10 proteins. At the functional level, EC-EV mediated inflammation and promoted the adhesion and migration of THP-1. Taken together, our findings proved that the EV released from inflamed EC were enriched with a cocktail of inflammatory markers, chemokines, and cytokines which are able to establish a targeted cross-talk between EC and monocytes and reprogramming them toward a pro- or anti-inflammatory phenotypes.

Project description:IntroductionAs with any other radial glia in the central nervous system, Müller glia derive from the same neuroepithelial precursors, perform similar functions, and exhibit neurogenic properties as radial glia in the brain. Müller glial cells retain progenitor-like characteristics in the adult human eye and can partially restore visual function upon intravitreal transplantation into animal models of glaucoma. Recently, it has been demonstrated that intracellular communication is possible via the secretion of nano-sized membrane-bound extracellular vesicles (EV), which contain bioactive molecules like microRNA (miRNA) and proteins that induce phenotypic changes when internalised by recipient cells.MethodsWe conducted high-throughput sequencing to profile the microRNA signature of EV populations secreted by Müller glia in culture and used bioinformatics tools to evaluate their potential role in the neuroprotective signalling attributed to these cells.ResultsSequencing of miRNA within Müller EV suggested enrichment with species associated with stem cells such as miR-21 and miR-16, as well as with miRNA previously found to play a role in diverse Müller cell functions in the retina: miR-9, miR-125b, and the let-7 family. A total of 51 miRNAs were found to be differentially enriched in EV compared to the whole cells from which EV originated. Bioinformatics analyses also indicated that preferential enrichment of species was demonstrated to regulate genes involved in cell proliferation and survival, including PTEN, the master inhibitor of the PI3K/AKT pathway.DiscussionThe results suggest that the release by Müller cells of miRNA-enriched EV abundant in species that regulate anti-apoptotic signalling networks is likely to represent a significant proportion of the neuroprotective effect observed after the transplantation of these cells into animal models of retinal ganglion cell (RGC) depletion. Future studies will seek to evaluate the modulation of putative genes as well as the activation of these pathways in in vitro and in vivo models following the internalisation of Müller-EV by target retinal neurons.

Dataset Information

Endothelial Cell Morphology Regulates Inflammatory Cells Through MicroRNA Transferred by Extracellular Vesicles.

Publications

Endothelial Cell Morphology Regulates Inflammatory Cells Through MicroRNA Transferred by Extracellular Vesicles.

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