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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2018.01328

Anthraquinone Emodin Inhibits Tumor Necrosis Factor Alpha-induced Calcification of Human Aortic Valve Interstitial Cells via the NF-κB Pathway

 Kang Xu1*, Tingwen Zhou1, Yuming Huang1, Qingjia Chi2, Jiawei Shi1, Peng Zhu1* and Nianguo Dong1*
  • 1Huazhong University of Science and Technology, China
  • 2Wuhan University of Technology, China

Exploring effective therapies for delaying calcific heart valve disease (CHVD) is the focus of current cardiovascular clinical and scientific research. In this study, human aortic valve interstitial cells (hVICs) were isolated from patients with CHVD. After expansion, cultured hVICs were induced with the tumor necrosis factor-alpha (TNF-α) with or without anthraquinone emodin (EMD) treatments. Cytotoxicity and flow cytometric analysis were used to assess cell growth, while Alizarin Red S staining was used to detect hVICs calcification. Furthermore, RNA-sequencing analysis was utilized to investigate changes in mRNA profiles of cells cultured in TNF-α conditioned medium with or without EMD. Western blotting and qRT-PCR analyses were used for the verification of key selected genes. Our results indicated that EMD had limited influence on hVIC morphology, whereas in a dose-dependent fashion, EMD interfered with hVIC growth under TNF-α conditioned cell culture. Additionally, hVICs treated with TNF-α plus EMD, presented a gradual decrease of positive Alizarin Red S staining, when compared with cells treated with TNF-α only. Notably, cells treated with TNF-α plus EMD showed 1874 differential expression genes (DEGs), among them, 1131 were upregulated and 743 were downregulated. These DEGs displayed an enrichment of biological functions and signaling pathways, among them, BMP2, RELA, TNF, and TRAF1, were found to be significantly suppressed by EMD and selected given their role in mediating hVIC calcification. In conclusion, our study shows that EMD inhibits TNF-α-induced calcification and phenotypical transformation of hVICs via the NF-κB signaling pathway, thereby preventing calcification events stimulated during acute inflammatory responses.

Keywords: Calcific aortic valve disease, Anthraquinone, NF-κB, Bioinformatic analysis, anti-inflammation

Received: 29 Aug 2018; Accepted: 29 Oct 2018.

Edited by:

Cheorl-Ho Kim, Sungkyunkwan University, South Korea

Reviewed by:

He-Hui Xie, School of Medicine, Shanghai Jiao Tong University, China
Haolong Liu, Peking University Health Science Centre, China  

Copyright: © 2018 Xu, Zhou, Huang, Chi, Shi, Zhu and Dong. 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.

* Correspondence:
Dr. Kang Xu, Huazhong University of Science and Technology, Wuhan, China,
Dr. Peng Zhu, Huazhong University of Science and Technology, Wuhan, China,
Prof. Nianguo Dong, Huazhong University of Science and Technology, Wuhan, China,