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Mechanistic Roles of Matrilin-2 and Klotho in Modulating the Inflammatory Activity of Human Aortic Valve Cells
Background: Calcific aortic valve disease (CAVD) is a chronic inflammatory disease. Soluble extracellular matrix (ECM) proteins can act as damage-associated molecular patterns and may induce valvular inflammation. Matrilin-2 is an ECM protein and has been found to elevate the pro-osteogenic activity...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072362/ https://www.ncbi.nlm.nih.gov/pubmed/32046115 http://dx.doi.org/10.3390/cells9020385 |
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author | The, Erlinda Yao, Qingzhou Zhang, Peijian Zhai, Yufeng Ao, Lihua Fullerton, David A. Meng, Xianzhong |
author_facet | The, Erlinda Yao, Qingzhou Zhang, Peijian Zhai, Yufeng Ao, Lihua Fullerton, David A. Meng, Xianzhong |
author_sort | The, Erlinda |
collection | PubMed |
description | Background: Calcific aortic valve disease (CAVD) is a chronic inflammatory disease. Soluble extracellular matrix (ECM) proteins can act as damage-associated molecular patterns and may induce valvular inflammation. Matrilin-2 is an ECM protein and has been found to elevate the pro-osteogenic activity in human aortic valve interstitial cells (AVICs). Klotho, an anti-aging protein, appears to have anti-inflammatory properties. The effect of matrilin-2 and Klotho on AVIC inflammatory responses remains unclear. Methods and Results: Isolated human AVICs were exposed to matrilin-2. Soluble matrilin-2 induced the production of ICAM-1, MCP-1, and IL-6. It also induced protein kinase R (PKR) activation via Toll-like receptor (TLR) 2 and 4. Pretreatment with PKR inhibitors inhibited NF-κB activation and inflammatory mediator production induced by matrilin-2. Further, recombinant Klotho suppressed PKR and NF-κB activation and markedly reduced the production of inflammatory mediators in human AVICs exposed to matrilin-2. Conclusions: This study revealed that soluble matrilin-2 upregulates AVIC inflammatory activity via activation of the TLR-PKR-NF-κB pathway and that Klotho is potent to suppress AVIC inflammatory responses to a soluble ECM protein through inhibiting PKR. These novel findings indicate that soluble matrilin-2 may accelerate the progression of CAVD by inducing valvular inflammation and that Klotho has the potential to suppress valvular inflammation. |
format | Online Article Text |
id | pubmed-7072362 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-70723622020-03-19 Mechanistic Roles of Matrilin-2 and Klotho in Modulating the Inflammatory Activity of Human Aortic Valve Cells The, Erlinda Yao, Qingzhou Zhang, Peijian Zhai, Yufeng Ao, Lihua Fullerton, David A. Meng, Xianzhong Cells Article Background: Calcific aortic valve disease (CAVD) is a chronic inflammatory disease. Soluble extracellular matrix (ECM) proteins can act as damage-associated molecular patterns and may induce valvular inflammation. Matrilin-2 is an ECM protein and has been found to elevate the pro-osteogenic activity in human aortic valve interstitial cells (AVICs). Klotho, an anti-aging protein, appears to have anti-inflammatory properties. The effect of matrilin-2 and Klotho on AVIC inflammatory responses remains unclear. Methods and Results: Isolated human AVICs were exposed to matrilin-2. Soluble matrilin-2 induced the production of ICAM-1, MCP-1, and IL-6. It also induced protein kinase R (PKR) activation via Toll-like receptor (TLR) 2 and 4. Pretreatment with PKR inhibitors inhibited NF-κB activation and inflammatory mediator production induced by matrilin-2. Further, recombinant Klotho suppressed PKR and NF-κB activation and markedly reduced the production of inflammatory mediators in human AVICs exposed to matrilin-2. Conclusions: This study revealed that soluble matrilin-2 upregulates AVIC inflammatory activity via activation of the TLR-PKR-NF-κB pathway and that Klotho is potent to suppress AVIC inflammatory responses to a soluble ECM protein through inhibiting PKR. These novel findings indicate that soluble matrilin-2 may accelerate the progression of CAVD by inducing valvular inflammation and that Klotho has the potential to suppress valvular inflammation. MDPI 2020-02-07 /pmc/articles/PMC7072362/ /pubmed/32046115 http://dx.doi.org/10.3390/cells9020385 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article The, Erlinda Yao, Qingzhou Zhang, Peijian Zhai, Yufeng Ao, Lihua Fullerton, David A. Meng, Xianzhong Mechanistic Roles of Matrilin-2 and Klotho in Modulating the Inflammatory Activity of Human Aortic Valve Cells |
title | Mechanistic Roles of Matrilin-2 and Klotho in Modulating the Inflammatory Activity of Human Aortic Valve Cells |
title_full | Mechanistic Roles of Matrilin-2 and Klotho in Modulating the Inflammatory Activity of Human Aortic Valve Cells |
title_fullStr | Mechanistic Roles of Matrilin-2 and Klotho in Modulating the Inflammatory Activity of Human Aortic Valve Cells |
title_full_unstemmed | Mechanistic Roles of Matrilin-2 and Klotho in Modulating the Inflammatory Activity of Human Aortic Valve Cells |
title_short | Mechanistic Roles of Matrilin-2 and Klotho in Modulating the Inflammatory Activity of Human Aortic Valve Cells |
title_sort | mechanistic roles of matrilin-2 and klotho in modulating the inflammatory activity of human aortic valve cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072362/ https://www.ncbi.nlm.nih.gov/pubmed/32046115 http://dx.doi.org/10.3390/cells9020385 |
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