Int J Med Sci 2020; 17(18):3065-3072. doi:10.7150/ijms.49533

Research Paper

IL-21 promotes osteoblastic differentiation of human valvular interstitial cells through the JAK3/STAT3 pathway

Zongtao Liu*, Yixuan Wang*, Jiawei Shi, Si Chen, Li Xu, Fei Li, Nianguo Dong

Department of Cardiovascular Surgery, Wuhan Union Hospital, Huazhong University of Science and Technology, Wuhan, China.
*These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Liu Z, Wang Y, Shi J, Chen S, Xu L, Li F, Dong N. IL-21 promotes osteoblastic differentiation of human valvular interstitial cells through the JAK3/STAT3 pathway. Int J Med Sci 2020; 17(18):3065-3072. doi:10.7150/ijms.49533. Available from https://www.medsci.org/v17p3065.htm

File import instruction

Abstract

Objectives: This study amied to whether IL-21 promotes osteoblast transdifferentiation of cultured human Valvular interstitial cells (VICs).

Methods: We first confirmed that IL-21 alters gene expression between CAVD aortic valve tissue and normal samples by immunohistochemistry, qPCR, and western blotting. VICs were cultured and treated with IL-21. Gene and protein expression levels of the osteoblastic markers ALP and Runx2, which can be blocked by specific JAK3 inhibitors and/or siRNA of STAT3, were measured.

Results: IL-21 expression was upregulated in calcified aortic valves and promotes osteogenic differentiation of human VICs. IL-21 accelerated VIC calcification through the JAK3/STAT3 pathway.

Conclusion: Our data suggest that IL-21 is a key factor in valve calcification and a promising candidate for targeted therapeutics for CAVD.

Keywords: calcific aortic valve disease, Valvular interstitial cells, IL-21, valvular calcification, JAK3, STAT3