Cargando…

circDENND1B Participates in the Antiatherosclerotic Effect of IL-1β Monoclonal Antibody in Mouse by Promoting Cholesterol Efflux via miR-17-5p/Abca1 Axis

Inflammation is a crucial mediator of atherosclerosis, and several therapeutic methods that focus on inflammatory cytokines, including interleukin-1β (IL-1β), have proven effective in preventing atherogenesis. Circular RNAs (circRNAs) are a subclass of non-coding RNAs (ncRNAs) that can exert critica...

Descripción completa

Detalles Bibliográficos
Autores principales: Xu, Fei, Shen, Li, Chen, Han, Wang, Rui, Zang, Tongtong, Qian, Juying, Ge, Junbo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116881/
https://www.ncbi.nlm.nih.gov/pubmed/33996813
http://dx.doi.org/10.3389/fcell.2021.652032
_version_ 1783691492124000256
author Xu, Fei
Shen, Li
Chen, Han
Wang, Rui
Zang, Tongtong
Qian, Juying
Ge, Junbo
author_facet Xu, Fei
Shen, Li
Chen, Han
Wang, Rui
Zang, Tongtong
Qian, Juying
Ge, Junbo
author_sort Xu, Fei
collection PubMed
description Inflammation is a crucial mediator of atherosclerosis, and several therapeutic methods that focus on inflammatory cytokines, including interleukin-1β (IL-1β), have proven effective in preventing atherogenesis. Circular RNAs (circRNAs) are a subclass of non-coding RNAs (ncRNAs) that can exert critical functions in the regulation of atherosclerosis. Here, using circRNA sequencing, we revealed that circRNA circDENND1B (mmu_circ_0000081) is a promising novel mediator of atherosclerosis in mouse. The expression of circDENND1B is negatively related to the progression of atherosclerosis and foam cell formation, and the upregulation of circDENND1B significantly alleviates foam cell formation induced by ox-LDL by promoting cholesterol efflux. Moreover, circDENND1B participates in the anti-atherosclerotic effect of IL-1β monoclonal antibody (IL-1β mAb), both in vivo and in vitro. With bioinformatic prediction and RNA pull-down assays, we determined that circDENND1B sponges mmu-miR-17-5p to promote Abca1 expression in cells treated with IL-1β mAb. Our study revealed that circDENND1B, a novel regulator of cholesterol efflux, is a potential therapeutic target in atherosclerosis and provides new insights into the interaction between inflammation and cholesterol transport.
format Online
Article
Text
id pubmed-8116881
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-81168812021-05-14 circDENND1B Participates in the Antiatherosclerotic Effect of IL-1β Monoclonal Antibody in Mouse by Promoting Cholesterol Efflux via miR-17-5p/Abca1 Axis Xu, Fei Shen, Li Chen, Han Wang, Rui Zang, Tongtong Qian, Juying Ge, Junbo Front Cell Dev Biol Cell and Developmental Biology Inflammation is a crucial mediator of atherosclerosis, and several therapeutic methods that focus on inflammatory cytokines, including interleukin-1β (IL-1β), have proven effective in preventing atherogenesis. Circular RNAs (circRNAs) are a subclass of non-coding RNAs (ncRNAs) that can exert critical functions in the regulation of atherosclerosis. Here, using circRNA sequencing, we revealed that circRNA circDENND1B (mmu_circ_0000081) is a promising novel mediator of atherosclerosis in mouse. The expression of circDENND1B is negatively related to the progression of atherosclerosis and foam cell formation, and the upregulation of circDENND1B significantly alleviates foam cell formation induced by ox-LDL by promoting cholesterol efflux. Moreover, circDENND1B participates in the anti-atherosclerotic effect of IL-1β monoclonal antibody (IL-1β mAb), both in vivo and in vitro. With bioinformatic prediction and RNA pull-down assays, we determined that circDENND1B sponges mmu-miR-17-5p to promote Abca1 expression in cells treated with IL-1β mAb. Our study revealed that circDENND1B, a novel regulator of cholesterol efflux, is a potential therapeutic target in atherosclerosis and provides new insights into the interaction between inflammation and cholesterol transport. Frontiers Media S.A. 2021-04-29 /pmc/articles/PMC8116881/ /pubmed/33996813 http://dx.doi.org/10.3389/fcell.2021.652032 Text en Copyright © 2021 Xu, Shen, Chen, Wang, Zang, Qian and Ge. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Xu, Fei
Shen, Li
Chen, Han
Wang, Rui
Zang, Tongtong
Qian, Juying
Ge, Junbo
circDENND1B Participates in the Antiatherosclerotic Effect of IL-1β Monoclonal Antibody in Mouse by Promoting Cholesterol Efflux via miR-17-5p/Abca1 Axis
title circDENND1B Participates in the Antiatherosclerotic Effect of IL-1β Monoclonal Antibody in Mouse by Promoting Cholesterol Efflux via miR-17-5p/Abca1 Axis
title_full circDENND1B Participates in the Antiatherosclerotic Effect of IL-1β Monoclonal Antibody in Mouse by Promoting Cholesterol Efflux via miR-17-5p/Abca1 Axis
title_fullStr circDENND1B Participates in the Antiatherosclerotic Effect of IL-1β Monoclonal Antibody in Mouse by Promoting Cholesterol Efflux via miR-17-5p/Abca1 Axis
title_full_unstemmed circDENND1B Participates in the Antiatherosclerotic Effect of IL-1β Monoclonal Antibody in Mouse by Promoting Cholesterol Efflux via miR-17-5p/Abca1 Axis
title_short circDENND1B Participates in the Antiatherosclerotic Effect of IL-1β Monoclonal Antibody in Mouse by Promoting Cholesterol Efflux via miR-17-5p/Abca1 Axis
title_sort circdennd1b participates in the antiatherosclerotic effect of il-1β monoclonal antibody in mouse by promoting cholesterol efflux via mir-17-5p/abca1 axis
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116881/
https://www.ncbi.nlm.nih.gov/pubmed/33996813
http://dx.doi.org/10.3389/fcell.2021.652032
work_keys_str_mv AT xufei circdennd1bparticipatesintheantiatheroscleroticeffectofil1bmonoclonalantibodyinmousebypromotingcholesteroleffluxviamir175pabca1axis
AT shenli circdennd1bparticipatesintheantiatheroscleroticeffectofil1bmonoclonalantibodyinmousebypromotingcholesteroleffluxviamir175pabca1axis
AT chenhan circdennd1bparticipatesintheantiatheroscleroticeffectofil1bmonoclonalantibodyinmousebypromotingcholesteroleffluxviamir175pabca1axis
AT wangrui circdennd1bparticipatesintheantiatheroscleroticeffectofil1bmonoclonalantibodyinmousebypromotingcholesteroleffluxviamir175pabca1axis
AT zangtongtong circdennd1bparticipatesintheantiatheroscleroticeffectofil1bmonoclonalantibodyinmousebypromotingcholesteroleffluxviamir175pabca1axis
AT qianjuying circdennd1bparticipatesintheantiatheroscleroticeffectofil1bmonoclonalantibodyinmousebypromotingcholesteroleffluxviamir175pabca1axis
AT gejunbo circdennd1bparticipatesintheantiatheroscleroticeffectofil1bmonoclonalantibodyinmousebypromotingcholesteroleffluxviamir175pabca1axis