Effective silencing of miR-126 after ischemic stroke by means of intravenous α-tocopherol–conjugated heteroduplex oligonucleotide in mice

Abstract Brain endothelial cells (BECs) are involved in the pathogenesis of ischemic stroke. Recently, several microRNAs (miRNAs) in BECs were reported to regulate the endothelial function in ischemic brain. Therefore, modulation of miRNAs in BECs by a therapeutic oligonucleotide to inhibit miRNA (a...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Motohiro Suzuki, Satoru Ishibashi, Eri Iwasawa, Takahiro Oguma, Yasuhiro Saito, Fuying Li, Shinichi Otsu, Keiko Ichinose, Kotaro Yoshioka, Tetsuya Nagata, Takanori Yokota
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cd3a4701aaf24ae883deb88aa6047607
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:cd3a4701aaf24ae883deb88aa6047607
record_format	dspace
spelling	oai:doaj.org-article:cd3a4701aaf24ae883deb88aa60476072021-12-02T15:22:56ZEffective silencing of miR-126 after ischemic stroke by means of intravenous α-tocopherol–conjugated heteroduplex oligonucleotide in mice10.1038/s41598-021-93666-y2045-2322https://doaj.org/article/cd3a4701aaf24ae883deb88aa60476072021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93666-yhttps://doaj.org/toc/2045-2322Abstract Brain endothelial cells (BECs) are involved in the pathogenesis of ischemic stroke. Recently, several microRNAs (miRNAs) in BECs were reported to regulate the endothelial function in ischemic brain. Therefore, modulation of miRNAs in BECs by a therapeutic oligonucleotide to inhibit miRNA (antimiR) could be a useful strategy for treating ischemic stroke. However, few attempts have been made to achieve this strategy via systemic route due to lack of efficient delivery-method toward BECs. Here, we have developed a new technology for delivering an antimiR into BECs and silencing miRNAs in BECs, using a mouse ischemic stroke model. We designed a heteroduplex oligonucleotide, comprising an antimiR against miRNA-126 (miR-126) known as the endothelial-specific miRNA and its complementary RNA, conjugated to α-tocopherol as a delivery ligand (Toc-HDO targeting miR-126). Intravenous administration of Toc-HDO targeting miR-126 remarkably suppressed miR-126 expression in ischemic brain of the model mice. In addition, we showed that Toc-HDO targeting miR-126 was delivered into BECs more efficiently than the parent antimiR in ischemic brain, and that it was delivered more effectively in ischemic brain than non-ischemic brain of this model mice. Our study highlights the potential of this technology as a new clinical therapeutic option for ischemic stroke.Motohiro SuzukiSatoru IshibashiEri IwasawaTakahiro OgumaYasuhiro SaitoFuying LiShinichi OtsuKeiko IchinoseKotaro YoshiokaTetsuya NagataTakanori YokotaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Motohiro Suzuki Satoru Ishibashi Eri Iwasawa Takahiro Oguma Yasuhiro Saito Fuying Li Shinichi Otsu Keiko Ichinose Kotaro Yoshioka Tetsuya Nagata Takanori Yokota Effective silencing of miR-126 after ischemic stroke by means of intravenous α-tocopherol–conjugated heteroduplex oligonucleotide in mice
description	Abstract Brain endothelial cells (BECs) are involved in the pathogenesis of ischemic stroke. Recently, several microRNAs (miRNAs) in BECs were reported to regulate the endothelial function in ischemic brain. Therefore, modulation of miRNAs in BECs by a therapeutic oligonucleotide to inhibit miRNA (antimiR) could be a useful strategy for treating ischemic stroke. However, few attempts have been made to achieve this strategy via systemic route due to lack of efficient delivery-method toward BECs. Here, we have developed a new technology for delivering an antimiR into BECs and silencing miRNAs in BECs, using a mouse ischemic stroke model. We designed a heteroduplex oligonucleotide, comprising an antimiR against miRNA-126 (miR-126) known as the endothelial-specific miRNA and its complementary RNA, conjugated to α-tocopherol as a delivery ligand (Toc-HDO targeting miR-126). Intravenous administration of Toc-HDO targeting miR-126 remarkably suppressed miR-126 expression in ischemic brain of the model mice. In addition, we showed that Toc-HDO targeting miR-126 was delivered into BECs more efficiently than the parent antimiR in ischemic brain, and that it was delivered more effectively in ischemic brain than non-ischemic brain of this model mice. Our study highlights the potential of this technology as a new clinical therapeutic option for ischemic stroke.
format	article
author	Motohiro Suzuki Satoru Ishibashi Eri Iwasawa Takahiro Oguma Yasuhiro Saito Fuying Li Shinichi Otsu Keiko Ichinose Kotaro Yoshioka Tetsuya Nagata Takanori Yokota
author_facet	Motohiro Suzuki Satoru Ishibashi Eri Iwasawa Takahiro Oguma Yasuhiro Saito Fuying Li Shinichi Otsu Keiko Ichinose Kotaro Yoshioka Tetsuya Nagata Takanori Yokota
author_sort	Motohiro Suzuki
title	Effective silencing of miR-126 after ischemic stroke by means of intravenous α-tocopherol–conjugated heteroduplex oligonucleotide in mice
title_short	Effective silencing of miR-126 after ischemic stroke by means of intravenous α-tocopherol–conjugated heteroduplex oligonucleotide in mice
title_full	Effective silencing of miR-126 after ischemic stroke by means of intravenous α-tocopherol–conjugated heteroduplex oligonucleotide in mice
title_fullStr	Effective silencing of miR-126 after ischemic stroke by means of intravenous α-tocopherol–conjugated heteroduplex oligonucleotide in mice
title_full_unstemmed	Effective silencing of miR-126 after ischemic stroke by means of intravenous α-tocopherol–conjugated heteroduplex oligonucleotide in mice
title_sort	effective silencing of mir-126 after ischemic stroke by means of intravenous α-tocopherol–conjugated heteroduplex oligonucleotide in mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/cd3a4701aaf24ae883deb88aa6047607
work_keys_str_mv	AT motohirosuzuki effectivesilencingofmir126afterischemicstrokebymeansofintravenousatocopherolconjugatedheteroduplexoligonucleotideinmice AT satoruishibashi effectivesilencingofmir126afterischemicstrokebymeansofintravenousatocopherolconjugatedheteroduplexoligonucleotideinmice AT eriiwasawa effectivesilencingofmir126afterischemicstrokebymeansofintravenousatocopherolconjugatedheteroduplexoligonucleotideinmice AT takahirooguma effectivesilencingofmir126afterischemicstrokebymeansofintravenousatocopherolconjugatedheteroduplexoligonucleotideinmice AT yasuhirosaito effectivesilencingofmir126afterischemicstrokebymeansofintravenousatocopherolconjugatedheteroduplexoligonucleotideinmice AT fuyingli effectivesilencingofmir126afterischemicstrokebymeansofintravenousatocopherolconjugatedheteroduplexoligonucleotideinmice AT shinichiotsu effectivesilencingofmir126afterischemicstrokebymeansofintravenousatocopherolconjugatedheteroduplexoligonucleotideinmice AT keikoichinose effectivesilencingofmir126afterischemicstrokebymeansofintravenousatocopherolconjugatedheteroduplexoligonucleotideinmice AT kotaroyoshioka effectivesilencingofmir126afterischemicstrokebymeansofintravenousatocopherolconjugatedheteroduplexoligonucleotideinmice AT tetsuyanagata effectivesilencingofmir126afterischemicstrokebymeansofintravenousatocopherolconjugatedheteroduplexoligonucleotideinmice AT takanoriyokota effectivesilencingofmir126afterischemicstrokebymeansofintravenousatocopherolconjugatedheteroduplexoligonucleotideinmice
_version_	1718387401416507392

Effective silencing of miR-126 after ischemic stroke by means of intravenous α-tocopherol–conjugated heteroduplex oligonucleotide in mice

Ejemplares similares