The effects of exosomes derived from trabecular meshwork cells on Schlemm’s canal endothelial cells

Abstract Trabecular meshwork (TM) and Schlemm’s canal (SC) are the main structures within the conventional outflow pathway, and TM cells and SC endothelial (SCE) cells are essential for controlling intraocular pressure. To examine the interaction between TM cells and SCE cells, we investigated wheth...

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Autores principales:	Eri Takahashi, Junji Saruwatari, Tomokazu Fujimoto, Yuki Tanoue, Takaichi Fukuda, Toshihiro Inoue
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cdf27d5eb87244a4a49228c988447801
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spelling	oai:doaj.org-article:cdf27d5eb87244a4a49228c9884478012021-11-14T12:23:15ZThe effects of exosomes derived from trabecular meshwork cells on Schlemm’s canal endothelial cells10.1038/s41598-021-01450-92045-2322https://doaj.org/article/cdf27d5eb87244a4a49228c9884478012021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01450-9https://doaj.org/toc/2045-2322Abstract Trabecular meshwork (TM) and Schlemm’s canal (SC) are the main structures within the conventional outflow pathway, and TM cells and SC endothelial (SCE) cells are essential for controlling intraocular pressure. To examine the interaction between TM cells and SCE cells, we investigated whether exosomes contribute to intercellular communication. Additionally, TM cells in glaucoma acquire mesenchymal characteristics in response to transforming growth factor (TGF)-β2 and extracellular matrix proteins such as collagen type 1 (Col-1); these changes result in increased resistance of aqueous outflow. In this study, we stimulated TM cells with TGF-β2 and Col-1 and characterized the exosomal miRNAs (exomiRs) released in response to each stimulus. Isolated exosomes were rich in miRNAs, with downregulated miR-23a-5p and upregulated miR-3942-5p and miR-7515 levels following Col-1 or TGF-β2 stimulation. Next, a miRNA-mRNA network under TGF-β2 stimulation was constructed. There were no connections among the 3 miRNAs and predicted genes under Col-1 stimulation. GO and KEGG analyses revealed that the identified miRNAs were associated with various signaling pathways, including the inflammatory response. Interestingly, SCE cells treated with miR-7515 mimic showed increased VEGFA, VEGFR2, PECAM, and Tie2 expression. Ultrastructures typical of exosomes and positive staining for exosomal markers were observed in human TM cells. Our data showed that TM cells may communicate with SCE cells via exomiRs and that miR-7515 may be important for SCE cell reprogramming.Eri TakahashiJunji SaruwatariTomokazu FujimotoYuki TanoueTakaichi FukudaToshihiro InoueNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Eri Takahashi Junji Saruwatari Tomokazu Fujimoto Yuki Tanoue Takaichi Fukuda Toshihiro Inoue The effects of exosomes derived from trabecular meshwork cells on Schlemm’s canal endothelial cells
description	Abstract Trabecular meshwork (TM) and Schlemm’s canal (SC) are the main structures within the conventional outflow pathway, and TM cells and SC endothelial (SCE) cells are essential for controlling intraocular pressure. To examine the interaction between TM cells and SCE cells, we investigated whether exosomes contribute to intercellular communication. Additionally, TM cells in glaucoma acquire mesenchymal characteristics in response to transforming growth factor (TGF)-β2 and extracellular matrix proteins such as collagen type 1 (Col-1); these changes result in increased resistance of aqueous outflow. In this study, we stimulated TM cells with TGF-β2 and Col-1 and characterized the exosomal miRNAs (exomiRs) released in response to each stimulus. Isolated exosomes were rich in miRNAs, with downregulated miR-23a-5p and upregulated miR-3942-5p and miR-7515 levels following Col-1 or TGF-β2 stimulation. Next, a miRNA-mRNA network under TGF-β2 stimulation was constructed. There were no connections among the 3 miRNAs and predicted genes under Col-1 stimulation. GO and KEGG analyses revealed that the identified miRNAs were associated with various signaling pathways, including the inflammatory response. Interestingly, SCE cells treated with miR-7515 mimic showed increased VEGFA, VEGFR2, PECAM, and Tie2 expression. Ultrastructures typical of exosomes and positive staining for exosomal markers were observed in human TM cells. Our data showed that TM cells may communicate with SCE cells via exomiRs and that miR-7515 may be important for SCE cell reprogramming.
format	article
author	Eri Takahashi Junji Saruwatari Tomokazu Fujimoto Yuki Tanoue Takaichi Fukuda Toshihiro Inoue
author_facet	Eri Takahashi Junji Saruwatari Tomokazu Fujimoto Yuki Tanoue Takaichi Fukuda Toshihiro Inoue
author_sort	Eri Takahashi
title	The effects of exosomes derived from trabecular meshwork cells on Schlemm’s canal endothelial cells
title_short	The effects of exosomes derived from trabecular meshwork cells on Schlemm’s canal endothelial cells
title_full	The effects of exosomes derived from trabecular meshwork cells on Schlemm’s canal endothelial cells
title_fullStr	The effects of exosomes derived from trabecular meshwork cells on Schlemm’s canal endothelial cells
title_full_unstemmed	The effects of exosomes derived from trabecular meshwork cells on Schlemm’s canal endothelial cells
title_sort	effects of exosomes derived from trabecular meshwork cells on schlemm’s canal endothelial cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/cdf27d5eb87244a4a49228c988447801
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The effects of exosomes derived from trabecular meshwork cells on Schlemm’s canal endothelial cells

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