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ER stress decreases exosome production through adiponectin/T-cadherin-dependent and -independent pathways

Exosomes, extracellular vesicles (EVs) produced within cells, mediate both the disposal of intracellular waste and communication with distant cells, and they are involved in a variety of disease processes. Although disease modifications of exosome cargos have been well studied, it has been poorly in...

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Autores principales: Fukuoka, Keita, Mineo, Ryohei, Kita, Shunbun, Fukuda, Shiro, Okita, Tomonori, Kawada-Horitani, Emi, Iioka, Masahito, Fujii, Kohei, Kawada, Keitaro, Fujishima, Yuya, Nishizawa, Hitoshi, Maeda, Norikazu, Shimomura, Iichiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10474463/
https://www.ncbi.nlm.nih.gov/pubmed/37524131
http://dx.doi.org/10.1016/j.jbc.2023.105114
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author Fukuoka, Keita
Mineo, Ryohei
Kita, Shunbun
Fukuda, Shiro
Okita, Tomonori
Kawada-Horitani, Emi
Iioka, Masahito
Fujii, Kohei
Kawada, Keitaro
Fujishima, Yuya
Nishizawa, Hitoshi
Maeda, Norikazu
Shimomura, Iichiro
author_facet Fukuoka, Keita
Mineo, Ryohei
Kita, Shunbun
Fukuda, Shiro
Okita, Tomonori
Kawada-Horitani, Emi
Iioka, Masahito
Fujii, Kohei
Kawada, Keitaro
Fujishima, Yuya
Nishizawa, Hitoshi
Maeda, Norikazu
Shimomura, Iichiro
author_sort Fukuoka, Keita
collection PubMed
description Exosomes, extracellular vesicles (EVs) produced within cells, mediate both the disposal of intracellular waste and communication with distant cells, and they are involved in a variety of disease processes. Although disease modifications of exosome cargos have been well studied, it has been poorly investigated how disease processes, such as endoplasmic reticulum (ER) stress, affect EV production. We previously reported that adiponectin, an adipocyte-secreted salutary factor, increases systemic exosome levels through T-cadherin-mediated enhancement of exosome biogenesis. In the present study, we demonstrated that adiponectin/T-cadherin-dependent EV production was susceptible to ER stress and that low-dose tunicamycin significantly reduced EV production in the presence, but not in the absence, of adiponectin. Moreover, pharmacological or genetic activation of inositol-requiring enzyme 1α, a central regulator of ER stress, downregulated T-cadherin at the mRNA and protein levels as well as attenuated EV production. In addition, adiponectin/T-cadherin-independent EV production was attenuated under ER stress conditions. Repeated administration of tunicamycin to mice decreased circulating small EVs without decreasing tissue T-cadherin expression. Mechanistically, inositol-requiring enzyme 1α activation by silencing of the X-box binding protein 1 transcription factor upregulated the canonical interferon pathway and decreased EV production. The interferon pathway, when it was activated by polyinosinic–polycytidylic acid, also significantly attenuated EV production. Thus, we concluded that ER stress decreases exosome production through adiponectin/T-cadherin-dependent and -independent pathways.
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spelling pubmed-104744632023-09-03 ER stress decreases exosome production through adiponectin/T-cadherin-dependent and -independent pathways Fukuoka, Keita Mineo, Ryohei Kita, Shunbun Fukuda, Shiro Okita, Tomonori Kawada-Horitani, Emi Iioka, Masahito Fujii, Kohei Kawada, Keitaro Fujishima, Yuya Nishizawa, Hitoshi Maeda, Norikazu Shimomura, Iichiro J Biol Chem Research Article Exosomes, extracellular vesicles (EVs) produced within cells, mediate both the disposal of intracellular waste and communication with distant cells, and they are involved in a variety of disease processes. Although disease modifications of exosome cargos have been well studied, it has been poorly investigated how disease processes, such as endoplasmic reticulum (ER) stress, affect EV production. We previously reported that adiponectin, an adipocyte-secreted salutary factor, increases systemic exosome levels through T-cadherin-mediated enhancement of exosome biogenesis. In the present study, we demonstrated that adiponectin/T-cadherin-dependent EV production was susceptible to ER stress and that low-dose tunicamycin significantly reduced EV production in the presence, but not in the absence, of adiponectin. Moreover, pharmacological or genetic activation of inositol-requiring enzyme 1α, a central regulator of ER stress, downregulated T-cadherin at the mRNA and protein levels as well as attenuated EV production. In addition, adiponectin/T-cadherin-independent EV production was attenuated under ER stress conditions. Repeated administration of tunicamycin to mice decreased circulating small EVs without decreasing tissue T-cadherin expression. Mechanistically, inositol-requiring enzyme 1α activation by silencing of the X-box binding protein 1 transcription factor upregulated the canonical interferon pathway and decreased EV production. The interferon pathway, when it was activated by polyinosinic–polycytidylic acid, also significantly attenuated EV production. Thus, we concluded that ER stress decreases exosome production through adiponectin/T-cadherin-dependent and -independent pathways. American Society for Biochemistry and Molecular Biology 2023-07-29 /pmc/articles/PMC10474463/ /pubmed/37524131 http://dx.doi.org/10.1016/j.jbc.2023.105114 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Fukuoka, Keita
Mineo, Ryohei
Kita, Shunbun
Fukuda, Shiro
Okita, Tomonori
Kawada-Horitani, Emi
Iioka, Masahito
Fujii, Kohei
Kawada, Keitaro
Fujishima, Yuya
Nishizawa, Hitoshi
Maeda, Norikazu
Shimomura, Iichiro
ER stress decreases exosome production through adiponectin/T-cadherin-dependent and -independent pathways
title ER stress decreases exosome production through adiponectin/T-cadherin-dependent and -independent pathways
title_full ER stress decreases exosome production through adiponectin/T-cadherin-dependent and -independent pathways
title_fullStr ER stress decreases exosome production through adiponectin/T-cadherin-dependent and -independent pathways
title_full_unstemmed ER stress decreases exosome production through adiponectin/T-cadherin-dependent and -independent pathways
title_short ER stress decreases exosome production through adiponectin/T-cadherin-dependent and -independent pathways
title_sort er stress decreases exosome production through adiponectin/t-cadherin-dependent and -independent pathways
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10474463/
https://www.ncbi.nlm.nih.gov/pubmed/37524131
http://dx.doi.org/10.1016/j.jbc.2023.105114
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