Cargando…

Berberine Regulated miR150-5p to Inhibit P2X7 Receptor, EMMPRIN and MMP-9 Expression in oxLDL Induced Macrophages

Elevated extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase-9 (MMP-9) in oxidized low density lipoprotein (oxLDL)-induced macrophages leads to the progression of vulnerable plaques by degradation of the extracellular matrix. Our previous report showed that berberin...

Descripción completa

Detalles Bibliográficos
Autores principales: Lu, Lin, Huang, Jianjian, Xue, Xia, Wang, Ting, Huang, Zhouqing, Li, Jianmin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093865/
https://www.ncbi.nlm.nih.gov/pubmed/33959010
http://dx.doi.org/10.3389/fphar.2021.639558
_version_ 1783687903571869696
author Lu, Lin
Huang, Jianjian
Xue, Xia
Wang, Ting
Huang, Zhouqing
Li, Jianmin
author_facet Lu, Lin
Huang, Jianjian
Xue, Xia
Wang, Ting
Huang, Zhouqing
Li, Jianmin
author_sort Lu, Lin
collection PubMed
description Elevated extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase-9 (MMP-9) in oxidized low density lipoprotein (oxLDL)-induced macrophages leads to the progression of vulnerable plaques by degradation of the extracellular matrix. Our previous report showed that berberine regulates the expression of both EMMPRIN and MMP-9. In addition, P2X7 receptor (P2X7R) upregulation plays a crucial role in the development of atherosclerosis. However, it is unclear whether berberine regulated P2X7R level to inhibit both EMMPRIN and MMP-9 expession in macrophages. In the present study, we investigated the impact of berberine on P2X7R expression and the regulation of P2X7R in the expression of EMMPRIN and MMP-9 in oxLDL-induced macrophages. We found that P2X7R expression was increased, miR150-5p was reduced in oxLDL-induced macrophages, relatively. And A-438079 (a P2X7R inhibitor) or miR150-5p mimic treatment greatly reversed the upregulation of EMMPRIN and MMP-9 expression. Moreover, A-438079 significantly reduced oxLDL-induced AMP-activated protein kinase-α (AMPK-α) phosphorylation and reversed the activation of mitogen-activated protein kinase (MAPK), which in turn decreased the expression of EMMPRIN and MMP-9. These findings illustrate that P2X7R suppresses EMMPRIN and MMP-9 expression by inhibiting the AMPK-α/MAPK pathway in oxLDL-induced macrophages. Accordingly, exposure to berberine markedly upregulated miR150-5p, decreased P2X7R expression and downregulated MMP-9 and EMMPRIN levels in oxLDL-induced macrophages, resulting in AMPK-α/MAPK (JNK, p38, and ERK) inactivation. Overall, these results indicate that berberine increased miR150-5p level, subsequently inhibits P2X7R-mediated EMMPRIN and MMP-9 expression by suppressing AMPK-α and MAPK signaling in oxLDL-induced macrophages.
format Online
Article
Text
id pubmed-8093865
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-80938652021-05-05 Berberine Regulated miR150-5p to Inhibit P2X7 Receptor, EMMPRIN and MMP-9 Expression in oxLDL Induced Macrophages Lu, Lin Huang, Jianjian Xue, Xia Wang, Ting Huang, Zhouqing Li, Jianmin Front Pharmacol Pharmacology Elevated extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase-9 (MMP-9) in oxidized low density lipoprotein (oxLDL)-induced macrophages leads to the progression of vulnerable plaques by degradation of the extracellular matrix. Our previous report showed that berberine regulates the expression of both EMMPRIN and MMP-9. In addition, P2X7 receptor (P2X7R) upregulation plays a crucial role in the development of atherosclerosis. However, it is unclear whether berberine regulated P2X7R level to inhibit both EMMPRIN and MMP-9 expession in macrophages. In the present study, we investigated the impact of berberine on P2X7R expression and the regulation of P2X7R in the expression of EMMPRIN and MMP-9 in oxLDL-induced macrophages. We found that P2X7R expression was increased, miR150-5p was reduced in oxLDL-induced macrophages, relatively. And A-438079 (a P2X7R inhibitor) or miR150-5p mimic treatment greatly reversed the upregulation of EMMPRIN and MMP-9 expression. Moreover, A-438079 significantly reduced oxLDL-induced AMP-activated protein kinase-α (AMPK-α) phosphorylation and reversed the activation of mitogen-activated protein kinase (MAPK), which in turn decreased the expression of EMMPRIN and MMP-9. These findings illustrate that P2X7R suppresses EMMPRIN and MMP-9 expression by inhibiting the AMPK-α/MAPK pathway in oxLDL-induced macrophages. Accordingly, exposure to berberine markedly upregulated miR150-5p, decreased P2X7R expression and downregulated MMP-9 and EMMPRIN levels in oxLDL-induced macrophages, resulting in AMPK-α/MAPK (JNK, p38, and ERK) inactivation. Overall, these results indicate that berberine increased miR150-5p level, subsequently inhibits P2X7R-mediated EMMPRIN and MMP-9 expression by suppressing AMPK-α and MAPK signaling in oxLDL-induced macrophages. Frontiers Media S.A. 2021-04-20 /pmc/articles/PMC8093865/ /pubmed/33959010 http://dx.doi.org/10.3389/fphar.2021.639558 Text en Copyright © 2021 Lu, Huang, Xue, Wang, Huang and Li. 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 Pharmacology
Lu, Lin
Huang, Jianjian
Xue, Xia
Wang, Ting
Huang, Zhouqing
Li, Jianmin
Berberine Regulated miR150-5p to Inhibit P2X7 Receptor, EMMPRIN and MMP-9 Expression in oxLDL Induced Macrophages
title Berberine Regulated miR150-5p to Inhibit P2X7 Receptor, EMMPRIN and MMP-9 Expression in oxLDL Induced Macrophages
title_full Berberine Regulated miR150-5p to Inhibit P2X7 Receptor, EMMPRIN and MMP-9 Expression in oxLDL Induced Macrophages
title_fullStr Berberine Regulated miR150-5p to Inhibit P2X7 Receptor, EMMPRIN and MMP-9 Expression in oxLDL Induced Macrophages
title_full_unstemmed Berberine Regulated miR150-5p to Inhibit P2X7 Receptor, EMMPRIN and MMP-9 Expression in oxLDL Induced Macrophages
title_short Berberine Regulated miR150-5p to Inhibit P2X7 Receptor, EMMPRIN and MMP-9 Expression in oxLDL Induced Macrophages
title_sort berberine regulated mir150-5p to inhibit p2x7 receptor, emmprin and mmp-9 expression in oxldl induced macrophages
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093865/
https://www.ncbi.nlm.nih.gov/pubmed/33959010
http://dx.doi.org/10.3389/fphar.2021.639558
work_keys_str_mv AT lulin berberineregulatedmir1505ptoinhibitp2x7receptoremmprinandmmp9expressioninoxldlinducedmacrophages
AT huangjianjian berberineregulatedmir1505ptoinhibitp2x7receptoremmprinandmmp9expressioninoxldlinducedmacrophages
AT xuexia berberineregulatedmir1505ptoinhibitp2x7receptoremmprinandmmp9expressioninoxldlinducedmacrophages
AT wangting berberineregulatedmir1505ptoinhibitp2x7receptoremmprinandmmp9expressioninoxldlinducedmacrophages
AT huangzhouqing berberineregulatedmir1505ptoinhibitp2x7receptoremmprinandmmp9expressioninoxldlinducedmacrophages
AT lijianmin berberineregulatedmir1505ptoinhibitp2x7receptoremmprinandmmp9expressioninoxldlinducedmacrophages