Luteolin and apigenin activate the Oct-4/Sox2 signal via NFATc1 in human periodontal ligament cells
Luteolin and apigenin activate the Oct-4/Sox2 signal via NFATc1 in human periodontal ligament cells
复制标题
木犀草素和芹菜素通过人牙周膜细胞中的 NFATc1 激活 Oct-4/Sox2 信号。
DOI：
10.1002/cbin.10648
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发表时间：
2016-10-01
影响因子：
3.9
通讯作者：
Wei, Xi
中科院分区：
文献类型：
--
作者：
Liu, Lu;Peng, Zhengjun;Wei, Xi
鉴定小分子以激活Oct-4/Sox 2衍生的多能性网络代表了一种有希望的和安全的方法，无需遗传操作即可实现多能性。两种主要的生物活性黄酮类化合物木犀草素和芹菜素增强了重编程效率并增加了Oct-4/Sox 2/c-Myc的表达，尽管调控牙源性细胞多能性的详细机制仍不清楚。本研究通过观察木犀草素/芹菜素对牙周膜细胞（PDLCs）增殖、凋亡、Oct-4/Sox 2/c-Myc表达及多向分化的影响，探讨木犀草素/芹菜素对PDLCs增殖、凋亡及多向分化的影响。此外，我们分析了差异表达的多能性基因的PCR阵列。我们的结果表明，木犀草素/芹菜素抑制细胞增殖，增加凋亡，并阻止PDLCs在G2/M和S期。木犀草素和芹菜素激活Oct-4，Sox 2和c-Myc的表达在时间和剂量依赖性模式，并抑制谱系特异性分化。PCR芯片分析了木犀草素/芹菜素处理的PDLCs中的多个信号，其中NFATc 1是主要上调的基因。值得注意的是，用印加-6阻断NFATc 1信号显著降低了用毛地黄黄酮/芹菜素处理的PDLC中Oct-4、Sox 2和c-Myc的mRNA和蛋白表达，表明NFATc 1可能充当Oct-4/Sox 2信号的上游调节剂。总之，该研究表明，毛地黄黄酮和芹菜素通过NFATc 1激活Oct-4/Sox 2信号有效地维持PDLC的多能性。
Identifying small molecules to activate the Oct-4/Sox2-derived pluripotency network represents a hopeful and safe method to pluripotency without genetic manipulation. Luteolin and apigenin, two major bioactive flavonoids, enhance reprogramming efficiency and increase expression of Oct-4/Sox2/c-Myc, albeit the detailed mechanism regulating pluripotency in dental-derived cells remains unknown. In the present study, to elucidate the effect of luteolin/apigenin on pluripotency of periodontal ligament cells (PDLCs) through interaction with downstream signals, we examined cell cycle, proliferation, apoptosis, expression of Oct-4/Sox2/c-Myc, and multilineage differentiation of PDLCs with luteolin/apigenin treatment. Moreover, we profiled the differentially expressed pluripotency genes by PCR arrays. Our results demonstrated that luteolin/apigenin restrained cell proliferation, increased apoptosis, and arrested PDLCs in G2/M and S phase. Luteolin and apigenin activated expression of Oct-4, Sox2, and c-Myc in a time- and dose-dependent pattern, and repressed lineage-specific differentiation. PCR arrays profiled multiple signals in PDLCs with luteolin/apigenin treatment, among which NFATc1 was the major upregulated gene. Notably, blocking of the NFATc1 signal with INCA-6 significantly decreased mRNA and protein expression of Oct-4, Sox2, and c-Myc in PDLCs with luteolin/apigenin treatment, indicating that NFATc1 may act as an upstream modulator of Oct-4/Sox2 signal. Taken together, this study showed that luteolin and apigenin effectively maintain pluripotency of PDLCs through activation of Oct-4/Sox2 signal via NFATc1.