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Zingerone Attenuates Pi-induced Vascular Calcification via AMPK-mediated TIMP4 Expression
OBJECTIVE: Vascular calcification requires the differentiation of vascular smooth muscle cells (VSMCs) into osteoblast-like cells. This phenomenon can be enhanced by inflammation and oxidative stress. Zingerone is one of the active ingredients present in the ginger plant that has anti-inflammatory a...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Korean Society of Lipidology and Atherosclerosis
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838510/ https://www.ncbi.nlm.nih.gov/pubmed/33537254 http://dx.doi.org/10.12997/jla.2021.10.1.62 |
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author | Lim, Young-Ju Min, Hyeon-Young Jang, Won-Gu |
author_facet | Lim, Young-Ju Min, Hyeon-Young Jang, Won-Gu |
author_sort | Lim, Young-Ju |
collection | PubMed |
description | OBJECTIVE: Vascular calcification requires the differentiation of vascular smooth muscle cells (VSMCs) into osteoblast-like cells. This phenomenon can be enhanced by inflammation and oxidative stress. Zingerone is one of the active ingredients present in the ginger plant that has anti-inflammatory and antioxidant effects. Other functions include anti-obesity, anti-nausea effects. However, the functions of zingerone on vascular calcification has not yet been elucidated. This study investigated the effect of zingerone on vascular calcification and its molecular mechanism. METHODS: Reverse transcription-polymerase chain reaction (PCR), real-time PCR and Western blot analysis was used to measure expression levels of osteogenic marker genes and to investigate whether calcification was regulated by the expression of AMP-activated protein kinase (AMPK) and tissue inhibitor of metalloproteinase 4 (TIMP4). Alizarin red S staining was used to measure calcium deposition. Studies were carried out in VSMCs. RESULTS: Zingerone induced the expression of 2 markers of VSMCs differentiation (α-smooth muscle actin (α-SMA) and smooth muscle 22α (SM22α)) and decreased the expression of core-binding factor α-1 (CBFA1). Additionally, zingerone decreased inorganic phosphate (Pi)-induced expression of distal-less homeobox 5 and CBFA1. AMPK phosphorylation and TIMP4 expression were increased by zingerone. Importantly, zingerone protected VSMCs from calcification, and this protective effect was confirmed by increased TIMP4 via overexpression of AMPK, and inhibition of TIMP4 by Compound C. Zingerone upregulated AMPK/TIMP4 expression and recovered Pi-induced inhibition of TIMP4. CONCLUSIONS: Taken together, our results show that zingerone inhibits Pi-induced vascular calcification by regulating the AMPK/TIMP4 signaling cascade in VSMCs. These results suggest that the natural product zingerone could be useful for treating vascular and metabolic diseases. |
format | Online Article Text |
id | pubmed-7838510 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Korean Society of Lipidology and Atherosclerosis |
record_format | MEDLINE/PubMed |
spelling | pubmed-78385102021-02-02 Zingerone Attenuates Pi-induced Vascular Calcification via AMPK-mediated TIMP4 Expression Lim, Young-Ju Min, Hyeon-Young Jang, Won-Gu J Lipid Atheroscler Original Article OBJECTIVE: Vascular calcification requires the differentiation of vascular smooth muscle cells (VSMCs) into osteoblast-like cells. This phenomenon can be enhanced by inflammation and oxidative stress. Zingerone is one of the active ingredients present in the ginger plant that has anti-inflammatory and antioxidant effects. Other functions include anti-obesity, anti-nausea effects. However, the functions of zingerone on vascular calcification has not yet been elucidated. This study investigated the effect of zingerone on vascular calcification and its molecular mechanism. METHODS: Reverse transcription-polymerase chain reaction (PCR), real-time PCR and Western blot analysis was used to measure expression levels of osteogenic marker genes and to investigate whether calcification was regulated by the expression of AMP-activated protein kinase (AMPK) and tissue inhibitor of metalloproteinase 4 (TIMP4). Alizarin red S staining was used to measure calcium deposition. Studies were carried out in VSMCs. RESULTS: Zingerone induced the expression of 2 markers of VSMCs differentiation (α-smooth muscle actin (α-SMA) and smooth muscle 22α (SM22α)) and decreased the expression of core-binding factor α-1 (CBFA1). Additionally, zingerone decreased inorganic phosphate (Pi)-induced expression of distal-less homeobox 5 and CBFA1. AMPK phosphorylation and TIMP4 expression were increased by zingerone. Importantly, zingerone protected VSMCs from calcification, and this protective effect was confirmed by increased TIMP4 via overexpression of AMPK, and inhibition of TIMP4 by Compound C. Zingerone upregulated AMPK/TIMP4 expression and recovered Pi-induced inhibition of TIMP4. CONCLUSIONS: Taken together, our results show that zingerone inhibits Pi-induced vascular calcification by regulating the AMPK/TIMP4 signaling cascade in VSMCs. These results suggest that the natural product zingerone could be useful for treating vascular and metabolic diseases. Korean Society of Lipidology and Atherosclerosis 2021-01 2020-11-03 /pmc/articles/PMC7838510/ /pubmed/33537254 http://dx.doi.org/10.12997/jla.2021.10.1.62 Text en Copyright © 2021 The Korean Society of Lipid and Atherosclerosis. https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Lim, Young-Ju Min, Hyeon-Young Jang, Won-Gu Zingerone Attenuates Pi-induced Vascular Calcification via AMPK-mediated TIMP4 Expression |
title | Zingerone Attenuates Pi-induced Vascular Calcification via AMPK-mediated TIMP4 Expression |
title_full | Zingerone Attenuates Pi-induced Vascular Calcification via AMPK-mediated TIMP4 Expression |
title_fullStr | Zingerone Attenuates Pi-induced Vascular Calcification via AMPK-mediated TIMP4 Expression |
title_full_unstemmed | Zingerone Attenuates Pi-induced Vascular Calcification via AMPK-mediated TIMP4 Expression |
title_short | Zingerone Attenuates Pi-induced Vascular Calcification via AMPK-mediated TIMP4 Expression |
title_sort | zingerone attenuates pi-induced vascular calcification via ampk-mediated timp4 expression |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838510/ https://www.ncbi.nlm.nih.gov/pubmed/33537254 http://dx.doi.org/10.12997/jla.2021.10.1.62 |
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