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:
IL-21; JAK3; STAT3; Valvular interstitial cells; calcific aortic valve disease; valvular calcification.
© The author(s).
MeSH terms
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Adult
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Aortic Valve / cytology
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Aortic Valve / pathology*
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Aortic Valve Stenosis / pathology*
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Calcinosis / pathology*
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Case-Control Studies
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Cell Transdifferentiation / drug effects
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Cell Transdifferentiation / genetics
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Cells, Cultured
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Female
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Gene Knockdown Techniques
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Healthy Volunteers
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Humans
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Interleukin-21 Receptor alpha Subunit / genetics
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Interleukin-21 Receptor alpha Subunit / metabolism
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Interleukins / metabolism*
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Janus Kinase 3 / antagonists & inhibitors
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Janus Kinase 3 / metabolism
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Male
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Middle Aged
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Osteoblasts / pathology*
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Primary Cell Culture
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Quinazolines / pharmacology
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STAT3 Transcription Factor / genetics
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STAT3 Transcription Factor / metabolism
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Signal Transduction / drug effects
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Signal Transduction / genetics
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Up-Regulation
Substances
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IL21R protein, human
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Interleukin-21 Receptor alpha Subunit
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Interleukins
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Quinazolines
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STAT3 Transcription Factor
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STAT3 protein, human
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WHI P154
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JAK3 protein, human
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Janus Kinase 3
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interleukin-21
Supplementary concepts
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Aortic Valve, Calcification of