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作 者:王静[1] 康媛洁 赵龙[1] 王宁[1] 刘敏茹[1] WANG Jing;KANG Yuanjie;ZHAO Long;WANG Ning;LIU Minru(Respiratory Asthma Center,Xi’an Children’s Hospital,Xi’an,710003,China;Second Department of Respiratory Medicine,Xi’an Children’s Hospital,Xi’an,710003,China)
机构地区:[1]西安市儿童医院呼吸哮喘中心,西安市710003 [2]西安市儿童医院呼吸二科,西安市710003
出 处:《医学分子生物学杂志》2021年第6期496-500,共5页Journal of Medical Molecular Biology
摘 要:目的探究FOS样抗原1(FOS-like antigen 1,FOSL1)对哮喘中气道平滑肌细胞(airway smooth muscle cells,ASMCs)增殖与迁移的作用及其分子机制。方法建立TGF-β1诱导的ASMCs模型,并采用CCK-8试剂盒检测细胞活力。使用qRT-PCR和Western印迹方法检测FOSL1及ITGA6的表达量。MTT法、Transwell试验、qRT-PCR和Western印迹方法被用于测定ASMCs细胞增殖、迁移及其过程中关键蛋白的表达量。结果TGF-β1诱导下,ASMCs细胞中的FOSL1表达量上升。沉默FOSL1后,ASMCs细胞的增殖及迁移能力降低,并且细胞增殖过程中关键蛋白细胞核增殖因子及细胞核增殖抗原,迁移过程中关键蛋白基质金属蛋白酶-2及基质金属蛋白酶-9的表达量均显著降低。沉默FOSL1降低ITGA6的表达量。过表达ITGA6及IGF-1/SC79(PI3K/AKT信号通路激活剂)可部分程度上缓解沉默FOSL1导致的ASMCs细胞增殖及迁移能力的降低。结论FOSL1可通过ITGA6/PI3K/AKT通路调节气道平滑肌细胞的增殖及迁移能力,进而影响儿童呼吸哮喘的疾病进程。Objective To investigate the role of FOS-like antigen 1(FOSL1)in the proliferation and migration of airway smooth muscle cells(ASMCs)in asthma and the underlying molecular mechanisms.Methods The model of TGF-β1-induced ASMCs was constructed and CCK-8 assay kit was used to measure cell viability.The expression of FOSL1 and ITGA6 was detected by qRT-PCR and Western blotting.MTT assay,Transwell assay,qRT-PCR and Western blot analysis were employed to determine the proliferation,migration of ASMCs and the related proteins.Results The expression of FOSL1 was up-regulated in ASMCs after induction with TGF-β1.Silencing FOSL1 inhibited the proliferation and migration of ASMCs,and the expression levels of the related proteins,such as PCNA,Ki67,MMP-2 and MMP-9,were also down-regulated.Silencing FOSL1 decreased the expression level of ITGA6.Over-expressing ITGA6,IGF-1 or SC79 could partially reversed impaired cell proliferation and migration caused by FOSL1 silencing.Conclusion FOSL1 regulated the proliferation and migration of ASMCs via ITGA6/PI3K/AKT pathways,thereby influencing the progression of child asthma.
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