A nanodrug system overexpressed circRNA_0001805 alleviates nonalcoholic fatty liver disease via miR-106a-5p/miR-320a and ABCA1/CPT1 axis

A nanodrug system overexpressed circRNA_0001805 alleviates nonalcoholic fatty liver disease via miR-106a-5p/miR-320a and ABCA1/CPT1 axis

Abstract Our study aimed to explore the function of circRNA_0001805 in the pathogenesis of NAFLD and the underlying mechanism. A nanodrug system (GA-RM/GZ/PL) was constructed to overexpress circRNA_0001805 specifically in hepatocytes for the treatment of NAFLD. Fat droplet accumulation in cultured c...

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Autores principales: Jian Li, Jing Qi, Yishu Tang, Huaizheng Liu, Kefu Zhou, Zheren Dai, Lehong Yuan, Chuanzheng Sun
Formato: article
Lenguaje:EN
Publicado: BMC 2021
Materias:
circRNA_0001805
ABCA1
CPT1
Nanomedicine system
NAFLD
Biotechnology
TP248.13-248.65
Medical technology
R855-855.5
Acceso en línea:https://doaj.org/article/ecbfc5068be34d87a8baff79d45d3bb4
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spelling oai:doaj.org-article:ecbfc5068be34d87a8baff79d45d3bb42021-11-21T12:29:34ZA nanodrug system overexpressed circRNA_0001805 alleviates nonalcoholic fatty liver disease via miR-106a-5p/miR-320a and ABCA1/CPT1 axis10.1186/s12951-021-01108-81477-3155https://doaj.org/article/ecbfc5068be34d87a8baff79d45d3bb42021-11-01T00:00:00Zhttps://doi.org/10.1186/s12951-021-01108-8https://doaj.org/toc/1477-3155Abstract Our study aimed to explore the function of circRNA_0001805 in the pathogenesis of NAFLD and the underlying mechanism. A nanodrug system (GA-RM/GZ/PL) was constructed to overexpress circRNA_0001805 specifically in hepatocytes for the treatment of NAFLD. Fat droplet accumulation in cultured cells and mouse hepatic tissues was detected using Oil Red O or H&E staining. The relative expression of circRNAs, genes associated with lipogenesis was quantified by qRT-PCR. Interactions between circRNA_0001805 and miR-106a-5p/miR-320a, between miR-106a-5p/miR-320a and ABCA1/CPT1 were confirmed by dual-luciferase reporter assay. A novel metalorganic framework nanocarrier (GZ) was prepared from glycyrrhizic acid and zinc ions (Zn2+), and this nanocarrier was loaded with the circRNA_0001805 plasmid to construct a nanocore (GZ/PL). Then, this GZ/PL was coated with a galactose-modified RBC membrane (GA-RM) to generate GA-RM/GZ/PL. CircRNA_0001805 expression was downregulated in FFA-challenged primary hepatocytes, HFD-fed mice and NAFLD patients. Overexpressed circRNA_0001805 attenuated NAFLD development by suppressing lipid metabolism disorder and inflammation. CircRNA_0001805 targeted miR-106a-5p/miR-320a, which served as an upstream inhibitor of ABCA1/CPT1 and collaboratively regulated NAFLD progression. GA-RM/GZ/PL targeted hepatocytes, overexpressed circRNA_0001805, released glycyrrhizic acid to reduce the accumulation of lipids in the liver and played a synergistic role against NAFLD-induced lipid metabolism disorder. Graphical AbstractJian LiJing QiYishu TangHuaizheng LiuKefu ZhouZheren DaiLehong YuanChuanzheng SunBMCarticlecircRNA_0001805ABCA1CPT1Nanomedicine systemNAFLDBiotechnologyTP248.13-248.65Medical technologyR855-855.5ENJournal of Nanobiotechnology, Vol 19, Iss 1, Pp 1-21 (2021)
institution DOAJ
collection DOAJ
language EN
topic circRNA_0001805
ABCA1
CPT1
Nanomedicine system
NAFLD
Biotechnology
TP248.13-248.65
Medical technology
R855-855.5
spellingShingle circRNA_0001805
ABCA1
CPT1
Nanomedicine system
NAFLD
Biotechnology
TP248.13-248.65
Medical technology
R855-855.5
Jian Li
Jing Qi
Yishu Tang
Huaizheng Liu
Kefu Zhou
Zheren Dai
Lehong Yuan
Chuanzheng Sun
A nanodrug system overexpressed circRNA_0001805 alleviates nonalcoholic fatty liver disease via miR-106a-5p/miR-320a and ABCA1/CPT1 axis
description Abstract Our study aimed to explore the function of circRNA_0001805 in the pathogenesis of NAFLD and the underlying mechanism. A nanodrug system (GA-RM/GZ/PL) was constructed to overexpress circRNA_0001805 specifically in hepatocytes for the treatment of NAFLD. Fat droplet accumulation in cultured cells and mouse hepatic tissues was detected using Oil Red O or H&E staining. The relative expression of circRNAs, genes associated with lipogenesis was quantified by qRT-PCR. Interactions between circRNA_0001805 and miR-106a-5p/miR-320a, between miR-106a-5p/miR-320a and ABCA1/CPT1 were confirmed by dual-luciferase reporter assay. A novel metalorganic framework nanocarrier (GZ) was prepared from glycyrrhizic acid and zinc ions (Zn2+), and this nanocarrier was loaded with the circRNA_0001805 plasmid to construct a nanocore (GZ/PL). Then, this GZ/PL was coated with a galactose-modified RBC membrane (GA-RM) to generate GA-RM/GZ/PL. CircRNA_0001805 expression was downregulated in FFA-challenged primary hepatocytes, HFD-fed mice and NAFLD patients. Overexpressed circRNA_0001805 attenuated NAFLD development by suppressing lipid metabolism disorder and inflammation. CircRNA_0001805 targeted miR-106a-5p/miR-320a, which served as an upstream inhibitor of ABCA1/CPT1 and collaboratively regulated NAFLD progression. GA-RM/GZ/PL targeted hepatocytes, overexpressed circRNA_0001805, released glycyrrhizic acid to reduce the accumulation of lipids in the liver and played a synergistic role against NAFLD-induced lipid metabolism disorder. Graphical Abstract
format article
author Jian Li
Jing Qi
Yishu Tang
Huaizheng Liu
Kefu Zhou
Zheren Dai
Lehong Yuan
Chuanzheng Sun
author_facet Jian Li
Jing Qi
Yishu Tang
Huaizheng Liu
Kefu Zhou
Zheren Dai
Lehong Yuan
Chuanzheng Sun
author_sort Jian Li
title A nanodrug system overexpressed circRNA_0001805 alleviates nonalcoholic fatty liver disease via miR-106a-5p/miR-320a and ABCA1/CPT1 axis
title_short A nanodrug system overexpressed circRNA_0001805 alleviates nonalcoholic fatty liver disease via miR-106a-5p/miR-320a and ABCA1/CPT1 axis
title_full A nanodrug system overexpressed circRNA_0001805 alleviates nonalcoholic fatty liver disease via miR-106a-5p/miR-320a and ABCA1/CPT1 axis
title_fullStr A nanodrug system overexpressed circRNA_0001805 alleviates nonalcoholic fatty liver disease via miR-106a-5p/miR-320a and ABCA1/CPT1 axis
title_full_unstemmed A nanodrug system overexpressed circRNA_0001805 alleviates nonalcoholic fatty liver disease via miR-106a-5p/miR-320a and ABCA1/CPT1 axis
title_sort nanodrug system overexpressed circrna_0001805 alleviates nonalcoholic fatty liver disease via mir-106a-5p/mir-320a and abca1/cpt1 axis
publisher BMC
publishDate 2021
url https://doaj.org/article/ecbfc5068be34d87a8baff79d45d3bb4
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