Central role of cellular senescence in TSLP-induced airway remodeling in asthma.
Central role of cellular senescence in TSLP-induced airway remodeling in asthma.
复制标题
细胞衰老在 TSLP 诱导的哮喘气道重塑中的核心作用。
DOI：
10.1371/journal.pone.0077795
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Dong L
中科院分区：
文献类型：
--
作者：
Wu J;Dong F;Wang RA;Wang J;Zhao J;Yang M;Gong W;Cui R;Dong L
气道重塑是一种损伤后的修复过程，导致哮喘患者的气道高反应性增加。胸腺间质淋巴生成素(TSLP)是一种重要的细胞因子，在协调、维持和放大哮喘的炎症反应中起着关键作用。TSLP也是哮喘气道重塑的关键因素。探讨TSLP诱导的细胞衰老在体内外哮喘气道重塑中的作用。用免疫组织化学方法检测了哮喘患者肺组织细胞衰老和气道重塑。以衰老信号通路为靶点的小分子和shRNA方法被用来探讨细胞衰老在TSLP诱导的体外气道重塑中的作用。衰老相关β-半乳糖苷酶(SA-β-GAL)染色和BrdU比色法检测细胞衰老。此外，针对STAT3的抑制剂WP1066在哮喘小鼠模型中进行了评估，以确定抑制细胞衰老是否影响哮喘的气道重塑。在哮喘患者的呼吸道上皮细胞样本中检测到细胞衰老的激活，这是由检查点激活和细胞周期停滞所证明的。此外，TSLP诱导的细胞衰老是体外气道重塑所必需的。此外，一种小鼠哮喘模型表明，抑制细胞衰老可以阻止气道重塑，缓解气道阻力。TSLP刺激可诱导哮喘气道重塑过程中的细胞衰老。抑制细胞衰老的信号通路可克服TSLP诱导的气道重塑。
Airway remodeling is a repair process that occurs after injury resulting in increased airway hyper-responsiveness in asthma. Thymic stromal lymphopoietin (TSLP), a vital cytokine, plays a critical role in orchestrating, perpetuating and amplifying the inflammatory response in asthma. TSLP is also a critical factor in airway remodeling in asthma. To examine the role of TSLP-induced cellular senescence in airway remodeling of asthma in vitro and in vivo. Cellular senescence and airway remodeling were examined in lung specimens from patients with asthma using immunohischemical analysis. Both small molecule and shRNA approaches that target the senescent signaling pathways were used to explore the role of cellular senescence in TSLP-induced airway remodeling in vitro. Senescence-Associated β-galactosidase (SA-β-Gal) staining, and BrdU assays were used to detect cellular senescence. In addition, the Stat3-targeted inhibitor, WP1066, was evaluated in an asthma mouse model to determine if inhibiting cellular senescence influences airway remodeling in asthma. Activation of cellular senescence as evidenced by checkpoint activation and cell cycle arrest was detected in airway epithelia samples from patients with asthma. Furthermore, TSLP-induced cellular senescence was required for airway remodeling in vitro. In addition, a mouse asthma model indicates that inhibiting cellular senescence blocks airway remodeling and relieves airway resistance. TSLP stimulation can induce cellular senescence during airway remodeling in asthma. Inhibiting the signaling pathways of cellular senescence overcomes TSLP-induced airway remodeling.
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影响因子：
78.5
作者：
Collado, Manuel;Serrano, Manuel
通讯作者：
Serrano, Manuel
DOI：
10.1084/jem.20062211
发表时间：
2007-02-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Allakhverdi Z;Comeau MR;Jessup HK;Yoon BR;Brewer A;Chartier S;Paquette N;Ziegler SF;Sarfati M;Delespesse G
通讯作者：
Delespesse G
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DOI：
10.4049/jimmunol.1100355
发表时间：
2011-08-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kashyap M;Rochman Y;Spolski R;Samsel L;Leonard WJ
通讯作者：
Leonard WJ
影响因子：
13.6
作者：
Freund A;Orjalo AV;Desprez PY;Campisi J
通讯作者：
Campisi J
影响因子：
3.7
作者：
Chen ZG;Zhang TT;Li HT;Chen FH;Zou XL;Ji JZ;Chen H
通讯作者：
Chen H