Notch1 contributes to TNF-α-induced proliferation and migration of airway smooth muscle cells through regulation of the Hes1/PTEN axis
Notch1 contributes to TNF-α-induced proliferation and migration of airway smooth muscle cells through regulation of the Hes1/PTEN axis
复制标题
Notch1 通过调节 Hes1/PTEN 轴促进 TNF-α 诱导的气道平滑肌细胞增殖和迁移
DOI：
10.1016/j.intimp.2020.106911
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发表时间：
2020-11-01
影响因子：
5.6
通讯作者：
Liu, Yun
中科院分区：
文献类型：
--
作者：
Li, Xudong;Zou, Fan;Liu, Yun
NOTCH1参与了哮喘的发病机制。然而，Notch1在哮喘气道重塑过程中调节气道平滑肌(ASM)细胞增殖和迁移的作用尚不清楚。利用肿瘤坏死因子-α诱导的体外模型，我们报道了Notch1参与了肿瘤坏死因子-α诱导的ASM细胞的增殖和迁移。我们的结果表明，在暴露于肿瘤坏死因子-α的ASM细胞中，Notch1的表达显著上调。NOTCH1抑制显著抑制了肿瘤坏死因子-α诱导的ASM细胞增殖和迁移，而Notch1过表达则促进了相反的作用。此外，Notch1抑制可下调细胞中Notch-1胞内区(NICD)和Hes1的表达，上调PTEN的表达。值得注意的是，Hes1的过表达部分逆转了Notch1抑制介导的对肿瘤坏死因子-α诱导的ASM细胞增殖和迁移的抑制作用。此外，抑制Notch1对PTEN表达的促进作用明显被Hes1过表达所抑制。总体而言，这些发现表明，Notch1抑制通过调节Hes1/PTEN信号轴抑制了TNF-α诱导的ASM细胞的增殖和迁移，这一发现突显了Notch1/Hes1/PTEN参与调节哮喘的气道重塑。
Notch1 has been implicated in asthma pathogenesis. However, the function of Notch1 in regulating airway smooth muscle (ASM) cell proliferation and migration during airway remodeling of asthma remains unknown. Using an in vitro model induced by tumor necrosis factor (TNF)-alpha, we reported in this study that Notch1 participated in TNF-alpha-induced proliferation and migration of ASM cells. Our results demonstrated that Notch1 expression was significantly upregulated in ASM cells exposed to TNF-alpha. Notch1 inhibition significantly repressed TNF-alpha-induced ASM cell proliferation and migration, while Notch1 overexpression promoted the opposite effect. Moreover, Notch1 inhibition downregulated the expression of Notch-1 intracellular domain (NICD) and Hes1, while upregulated PTEN expression in TNF-alpha-exposed cells. Notably, Hes1 overexpression partially reversed the Notch1-inhibition-mediated inhibitory effect on TNF-alpha-induced ASM cell proliferation and migration. In addition, the promoting effect of Notch1 inhibition on PTEN expression was markedly abrogated by Hes1 overexpression. Overall, these findings demonstrated that Notch1 inhibition repressed TNF-alpha-induced ASM cell proliferation and migration by modulating the Hes1/PTEN signaling axis, a finding that highlights the involvement of Notch1/Hes1/PTEN in regulating airway remodeling of asthma.