Int J Med Sci 2020; 17(18):3065-3072. doi:10.7150/ijms.49533
IL-21 promotes osteoblastic differentiation of human valvular interstitial cells through the JAK3/STAT3 pathway
Department of Cardiovascular Surgery, Wuhan Union Hospital, Huazhong University of Science and Technology, Wuhan, China.
*These authors contributed equally to this work.
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
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