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Salvia miltiorrhiza-Derived Sal-miR-58 Induces Autophagy and Attenuates Inflammation in Vascular Smooth Muscle Cells

Autophagy is associated with the cytoprotection of physiological processes against inflammation and oxidative stress. Salvia miltiorrhiza possesses cardiovascular protective actions and has powerful anti-oxidative and anti-inflammatory effects; however, whether and how Salvia miltiorrhiza-derived mi...

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Autores principales: Qin, Yan, Zheng, Bin, Yang, Gao-shan, Yang, Hao-jie, Zhou, Jing, Yang, Zhan, Zhang, Xin-hua, Zhao, Hong-ye, Shi, Jian-hong, Wen, Jin-kun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360890/
https://www.ncbi.nlm.nih.gov/pubmed/32679544
http://dx.doi.org/10.1016/j.omtn.2020.06.015
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author Qin, Yan
Zheng, Bin
Yang, Gao-shan
Yang, Hao-jie
Zhou, Jing
Yang, Zhan
Zhang, Xin-hua
Zhao, Hong-ye
Shi, Jian-hong
Wen, Jin-kun
author_facet Qin, Yan
Zheng, Bin
Yang, Gao-shan
Yang, Hao-jie
Zhou, Jing
Yang, Zhan
Zhang, Xin-hua
Zhao, Hong-ye
Shi, Jian-hong
Wen, Jin-kun
author_sort Qin, Yan
collection PubMed
description Autophagy is associated with the cytoprotection of physiological processes against inflammation and oxidative stress. Salvia miltiorrhiza possesses cardiovascular protective actions and has powerful anti-oxidative and anti-inflammatory effects; however, whether and how Salvia miltiorrhiza-derived microRNAs (miRNAs) protect vascular smooth muscle cells (VSMCs) by inducing autophagy across species are unknown. We first screened and identified Sal-miR-58 from Salvia miltiorrhiza as a natural autophagy inducer. Synthetic Sal-miR-58 suppresses chronic angiotensin II (Ang II) infusion-induced abdominal aortic aneurysm (AAA) formation in mice, as well as induces autophagy in VSMCs and attenuates the inflammatory response elicited by Ang II in vivo and in vitro. Mechanistically, Sal-miR-58 downregulates Krüppel-like factor 3 (KLF3) expression through direct binding to the 3′ UTR of KLF3, which in turn relieves KLF3 repression of E3 ubiquitin ligase neural precursor cell-expressed developmentally downregulated 4-like (NEDD4L) expression, whereas NEDD4L upregulation increases the ubiquitination and degradation of the platelet isoform of phosphofructokinase (PFKP), subsequently leading to a decrease in the activation of Akt/mammalian target of rapamycin (mTOR) signaling and facilitating VSMC autophagy induced by Sal-miR-58 in the context of chronic Ang II stimulation and aneurysm formation. Our results provide the first evidence that plant-derived Sal-miR-58 induces autophagy and attenuates inflammation in VSMCs through cross-species modulation of the KLF3/NEDD4L/PFKP regulatory pathway.
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spelling pubmed-73608902020-07-20 Salvia miltiorrhiza-Derived Sal-miR-58 Induces Autophagy and Attenuates Inflammation in Vascular Smooth Muscle Cells Qin, Yan Zheng, Bin Yang, Gao-shan Yang, Hao-jie Zhou, Jing Yang, Zhan Zhang, Xin-hua Zhao, Hong-ye Shi, Jian-hong Wen, Jin-kun Mol Ther Nucleic Acids Article Autophagy is associated with the cytoprotection of physiological processes against inflammation and oxidative stress. Salvia miltiorrhiza possesses cardiovascular protective actions and has powerful anti-oxidative and anti-inflammatory effects; however, whether and how Salvia miltiorrhiza-derived microRNAs (miRNAs) protect vascular smooth muscle cells (VSMCs) by inducing autophagy across species are unknown. We first screened and identified Sal-miR-58 from Salvia miltiorrhiza as a natural autophagy inducer. Synthetic Sal-miR-58 suppresses chronic angiotensin II (Ang II) infusion-induced abdominal aortic aneurysm (AAA) formation in mice, as well as induces autophagy in VSMCs and attenuates the inflammatory response elicited by Ang II in vivo and in vitro. Mechanistically, Sal-miR-58 downregulates Krüppel-like factor 3 (KLF3) expression through direct binding to the 3′ UTR of KLF3, which in turn relieves KLF3 repression of E3 ubiquitin ligase neural precursor cell-expressed developmentally downregulated 4-like (NEDD4L) expression, whereas NEDD4L upregulation increases the ubiquitination and degradation of the platelet isoform of phosphofructokinase (PFKP), subsequently leading to a decrease in the activation of Akt/mammalian target of rapamycin (mTOR) signaling and facilitating VSMC autophagy induced by Sal-miR-58 in the context of chronic Ang II stimulation and aneurysm formation. Our results provide the first evidence that plant-derived Sal-miR-58 induces autophagy and attenuates inflammation in VSMCs through cross-species modulation of the KLF3/NEDD4L/PFKP regulatory pathway. American Society of Gene & Cell Therapy 2020-06-24 /pmc/articles/PMC7360890/ /pubmed/32679544 http://dx.doi.org/10.1016/j.omtn.2020.06.015 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Qin, Yan
Zheng, Bin
Yang, Gao-shan
Yang, Hao-jie
Zhou, Jing
Yang, Zhan
Zhang, Xin-hua
Zhao, Hong-ye
Shi, Jian-hong
Wen, Jin-kun
Salvia miltiorrhiza-Derived Sal-miR-58 Induces Autophagy and Attenuates Inflammation in Vascular Smooth Muscle Cells
title Salvia miltiorrhiza-Derived Sal-miR-58 Induces Autophagy and Attenuates Inflammation in Vascular Smooth Muscle Cells
title_full Salvia miltiorrhiza-Derived Sal-miR-58 Induces Autophagy and Attenuates Inflammation in Vascular Smooth Muscle Cells
title_fullStr Salvia miltiorrhiza-Derived Sal-miR-58 Induces Autophagy and Attenuates Inflammation in Vascular Smooth Muscle Cells
title_full_unstemmed Salvia miltiorrhiza-Derived Sal-miR-58 Induces Autophagy and Attenuates Inflammation in Vascular Smooth Muscle Cells
title_short Salvia miltiorrhiza-Derived Sal-miR-58 Induces Autophagy and Attenuates Inflammation in Vascular Smooth Muscle Cells
title_sort salvia miltiorrhiza-derived sal-mir-58 induces autophagy and attenuates inflammation in vascular smooth muscle cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360890/
https://www.ncbi.nlm.nih.gov/pubmed/32679544
http://dx.doi.org/10.1016/j.omtn.2020.06.015
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