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Proliferation of Vascular Smooth Muscle Cells under ox-LDL Is Regulated by Alismatis rhizoma Decoction via InhibitingERK1/2 and miR-17∼92a Cluster Activation
Context: Alismatis rhizome decoction (AD) exhibits antiatherosclerotic activities. The activity of AD against vascular smooth muscle cell (VSMC) proliferation remains unclear. Objective. The mechanisms and effects of AD on oxidized low-density lipoprotein (ox-LDL)-induced VSMC proliferation were exp...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463403/ https://www.ncbi.nlm.nih.gov/pubmed/32908568 http://dx.doi.org/10.1155/2020/7275246 |
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author | Shen, Julian Wei, Wei Wang, Xialei Yang, Jingda Lu, Lu Lv, Xinru Xue, Xiehua |
author_facet | Shen, Julian Wei, Wei Wang, Xialei Yang, Jingda Lu, Lu Lv, Xinru Xue, Xiehua |
author_sort | Shen, Julian |
collection | PubMed |
description | Context: Alismatis rhizome decoction (AD) exhibits antiatherosclerotic activities. The activity of AD against vascular smooth muscle cell (VSMC) proliferation remains unclear. Objective. The mechanisms and effects of AD on oxidized low-density lipoprotein (ox-LDL)-induced VSMC proliferation were explored. Materials and methods. The male SD rats were fed with AD (2.56 g/mL) or 0.9% NaCl by oral gavage 4 mL twice daily for 7 d. Then, AD-containing serum (ADcs) was collected. MTS assay was applied to measure the VSMC viability. The proliferation of VSMCs was detected by 5-bromodeoxyuridine (BrdU) immunocytochemistry. The microRNA (miRNA) profiling was performed, and the target genes of miRNAs were searched from the TargetScan 7.2 database. The expressions of matrix metalloproteinases-2/9 (MMP-2/9), cyclin D1/E, cyclin-dependent kinase inhibitor 1B (p27), extracellular regulated protein kinases 1/2 (ERK1/2), and ERK1/2 phosphorylation were examined by western blotting or quantitative reverse transcription PCR. Results. The ox-LDL-induced miR-17-92a expression promoted VSMC proliferation. AD and the ERK1/2 inhibitor U0126 (10 μmol/L) inhibited VSMC proliferation and reduced the overexpression of miR-17∼92a. AD was found to inhibit phosphorylation of ERK1/2 and reduced the expression of MMP-2/9 in VSMCs. The expression of cyclin D1/E was suppressed, and p27 was elevated following treatment with AD as well as ERK1/2 inhibitor. According to the TargetScan 7.2 database, the target genes of miR-17∼92a act on tissue inhibitors of metalloproteinases (TIMPs)-MMPs, p27/21 cyclins, and peroxisome-proliferator-activated receptor α (PPARα) ATP-binding cassette transporter (ABC) A1/G1, which are involved in the process of atherosclerosis. Conclusions. AD inhibits ox-LDL-induced VSMC proliferation via inhibiting ERK1/2 and miR-17∼92a activation. The results provide the multitarget mechanisms for application of AD in the treatment of atherosclerosis. It would be helpful to the treatment of cardiovascular and cerebral diseases. |
format | Online Article Text |
id | pubmed-7463403 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-74634032020-09-08 Proliferation of Vascular Smooth Muscle Cells under ox-LDL Is Regulated by Alismatis rhizoma Decoction via InhibitingERK1/2 and miR-17∼92a Cluster Activation Shen, Julian Wei, Wei Wang, Xialei Yang, Jingda Lu, Lu Lv, Xinru Xue, Xiehua Evid Based Complement Alternat Med Research Article Context: Alismatis rhizome decoction (AD) exhibits antiatherosclerotic activities. The activity of AD against vascular smooth muscle cell (VSMC) proliferation remains unclear. Objective. The mechanisms and effects of AD on oxidized low-density lipoprotein (ox-LDL)-induced VSMC proliferation were explored. Materials and methods. The male SD rats were fed with AD (2.56 g/mL) or 0.9% NaCl by oral gavage 4 mL twice daily for 7 d. Then, AD-containing serum (ADcs) was collected. MTS assay was applied to measure the VSMC viability. The proliferation of VSMCs was detected by 5-bromodeoxyuridine (BrdU) immunocytochemistry. The microRNA (miRNA) profiling was performed, and the target genes of miRNAs were searched from the TargetScan 7.2 database. The expressions of matrix metalloproteinases-2/9 (MMP-2/9), cyclin D1/E, cyclin-dependent kinase inhibitor 1B (p27), extracellular regulated protein kinases 1/2 (ERK1/2), and ERK1/2 phosphorylation were examined by western blotting or quantitative reverse transcription PCR. Results. The ox-LDL-induced miR-17-92a expression promoted VSMC proliferation. AD and the ERK1/2 inhibitor U0126 (10 μmol/L) inhibited VSMC proliferation and reduced the overexpression of miR-17∼92a. AD was found to inhibit phosphorylation of ERK1/2 and reduced the expression of MMP-2/9 in VSMCs. The expression of cyclin D1/E was suppressed, and p27 was elevated following treatment with AD as well as ERK1/2 inhibitor. According to the TargetScan 7.2 database, the target genes of miR-17∼92a act on tissue inhibitors of metalloproteinases (TIMPs)-MMPs, p27/21 cyclins, and peroxisome-proliferator-activated receptor α (PPARα) ATP-binding cassette transporter (ABC) A1/G1, which are involved in the process of atherosclerosis. Conclusions. AD inhibits ox-LDL-induced VSMC proliferation via inhibiting ERK1/2 and miR-17∼92a activation. The results provide the multitarget mechanisms for application of AD in the treatment of atherosclerosis. It would be helpful to the treatment of cardiovascular and cerebral diseases. Hindawi 2020-08-22 /pmc/articles/PMC7463403/ /pubmed/32908568 http://dx.doi.org/10.1155/2020/7275246 Text en Copyright © 2020 Julian Shen et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Shen, Julian Wei, Wei Wang, Xialei Yang, Jingda Lu, Lu Lv, Xinru Xue, Xiehua Proliferation of Vascular Smooth Muscle Cells under ox-LDL Is Regulated by Alismatis rhizoma Decoction via InhibitingERK1/2 and miR-17∼92a Cluster Activation |
title | Proliferation of Vascular Smooth Muscle Cells under ox-LDL Is Regulated by Alismatis rhizoma Decoction via InhibitingERK1/2 and miR-17∼92a Cluster Activation |
title_full | Proliferation of Vascular Smooth Muscle Cells under ox-LDL Is Regulated by Alismatis rhizoma Decoction via InhibitingERK1/2 and miR-17∼92a Cluster Activation |
title_fullStr | Proliferation of Vascular Smooth Muscle Cells under ox-LDL Is Regulated by Alismatis rhizoma Decoction via InhibitingERK1/2 and miR-17∼92a Cluster Activation |
title_full_unstemmed | Proliferation of Vascular Smooth Muscle Cells under ox-LDL Is Regulated by Alismatis rhizoma Decoction via InhibitingERK1/2 and miR-17∼92a Cluster Activation |
title_short | Proliferation of Vascular Smooth Muscle Cells under ox-LDL Is Regulated by Alismatis rhizoma Decoction via InhibitingERK1/2 and miR-17∼92a Cluster Activation |
title_sort | proliferation of vascular smooth muscle cells under ox-ldl is regulated by alismatis rhizoma decoction via inhibitingerk1/2 and mir-17∼92a cluster activation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463403/ https://www.ncbi.nlm.nih.gov/pubmed/32908568 http://dx.doi.org/10.1155/2020/7275246 |
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