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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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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 |
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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 |
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