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Curcumin inhibits calcification of human aortic valve interstitial cells by interfering NF‐κB, AKT, and ERK pathways
Author(s) -
Zhou Tingwen,
Wang Yongjun,
Liu Ming,
Huang Yuming,
Shi Jiawei,
Dong Nianguo,
Xu Kang
Publication year - 2020
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.6674
Subject(s) - runx2 , pi3k/akt/mtor pathway , protein kinase b , mapk/erk pathway , curcumin , small interfering rna , signal transduction , microbiology and biotechnology , phosphorylation , nf κb , p38 mitogen activated protein kinases , cancer research , biology , chemistry , biochemistry , transcription factor , rna , gene
The osteogenic differentiation of human aortic valve interstitial cells (hVICs) is the key cellular mechanism of calcified aortic valve disease (CAVD). This study aimed to explore how curcumin (CCM) inhibits the osteogenic differentiation of hVICs and elucidate the molecular mechanisms involved. In this study, CCM inhibited the osteogenic differentiation of hVICs under osteogenic medium (OM) conditions by reversing the OM‐induced increase in calcified nodule formation and osteogenesis‐specific markers (ALP and Runx2). RNA sequencing identified 475 common differentially expressed genes with Venn diagrams of the different groups. Kyoto Encyclopedia of Genes and Genomes enrichment revealed that the CCM inhibition of hVIC osteogenic differentiation was enriched in the NF‐κB, PI3K‐AKT, TNF, Jak‐STAT, and MAPK signaling pathways. In addition, CCM suppressed the phosphorylation of ERK, IκBα, AKT, and interfered with the translocation of P65 into the cell nucleus in hVICs under OM culture conditions. In conclusion, CCM inhibited the osteogenic differentiation of hVICs via interfering with the activation of NF‐κB/AKT/ERK signaling pathways. Our findings provide novel insights into a critical role for CCM in CAVD progression and shed new light on CCM‐directed therapeutics for CAVD.