SETD7 promotes TNF-α-induced proliferation and migration of airway smooth muscle cells in vitro through enhancing NF-κB/CD38 signaling
SETD7 promotes TNF-α-induced proliferation and migration of airway smooth muscle cells in vitro through enhancing NF-κB/CD38 signaling
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SETD7 通过增强 NF-κ B/CD38 信号传导促进 TNF-α 诱导的气道平滑肌细胞体外增殖和迁移
DOI：
10.1016/j.intimp.2019.04.043
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发表时间：
2019-07-01
影响因子：
5.6
通讯作者：
Liu, Yun
中科院分区：
文献类型：
--
作者：
Wu, Yuanyuan;Zou, Fan;Liu, Yun
炎症引起了气道壁中气道平滑肌（ASM）细胞的过度增殖和迁移，导致哮喘发病机理中的气道重塑。含有固定域的赖氨酸甲基转移酶7（SETD7）已成为炎症的关键调节剂之一。然而，setD7在调节炎症诱导的ASM细胞增殖和侵袭中的功能尚不清楚。在本研究中，我们旨在研究setD7在体外由肿瘤坏死因子（TNF）-Alpha引起的ASM细胞增殖和侵袭中的功能。我们的结果表明，在用TNF-α刺激的ASM细胞中，SETD7表达上调。沉默的SETD7显着降低了TNF-Alpha诱导的ASM细胞增殖和迁移，而SETD7过表达的效果相反。值得注意的是，沉默setD7降低了核因子（NF）-kappa B的激活，并降低了TNF-Alpha诱导的CD38的表达。阻断NF-kappa b激活显着消除了setD7过表达对CD38表达的促销效果。此外，CD38的过表达部分逆转了SetD7沉默对TNF-Alpha诱导的ASM细胞增殖和迁移的抑制作用。总体而言，这些结果表明，SETD7通过调节NF-KAPPA B/CD38信号传导调节TNF-Alpha诱导的ASM细胞增殖和迁移，这表明SETD7在哮喘Airway重塑中的潜在作用。
The inflammation-induced the excessive proliferation and migration of airway smooth muscle (ASM) cells in the airway wall contribute to airway remodeling in asthma pathogenesis. SET domain-containing lysine methyltransferase 7 (SETD7) has emerged as one of the key regulators of inflammation. Yet, the function of SETD7 in regulating inflammation-induced ASM cell proliferation and invasion remains unclear. In the present study, we aimed to investigate the function of SETD7 in regulating ASM cell proliferation and invasion induced by tumor necrosis factor (TNF)-alpha in vitro. Our results showed that SETD7 expression was upregulated in ASM cells stimulated with TNF-alpha. Silencing SETD7 significantly decreased TNF-alpha-induced ASM cell proliferation and migration, while SETD7 overexpression exhibited the opposite effect. Notably, silencing SETD7 decreased the activation of nuclear factor (NF)-kappa B and reduced the expression of CD38 induced by TNF-alpha. Blocking NF-kappa B activation significantly abrogated the promotional effect of SETD7 overexpression on CD38 expression. Moreover, overexpression of CD38 partially reversed the inhibitory effect of SETD7 silencing on TNF-alpha-induced ASM cell proliferation and migration. Overall, these results demonstrate that SETD7 regulates TNF-alpha-induced ASM cell proliferation and migration through modulation of NF-kappa B/CD38 signaling, suggesting a potential role of SETD7 in asthma airway remodeling.