Cryptotanshinone Attenuates Airway Remodeling by Inhibiting Crosstalk Between Tumor Necrosis Factor-Like Weak Inducer of Apoptosis and Transforming Growth Factor Beta 1 Signaling Pathways in Asthma
Cryptotanshinone Attenuates Airway Remodeling by Inhibiting Crosstalk Between Tumor Necrosis Factor-Like Weak Inducer of Apoptosis and Transforming Growth Factor Beta 1 Signaling Pathways in Asthma
复制标题
隐丹参酮通过抑制哮喘中肿瘤坏死因子样弱细胞凋亡诱导剂与转化生长因子 Beta 1 信号通路之间的串扰来减轻气道重塑。
DOI：
10.3389/fphar.2019.01338
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发表时间：
2019-11-11
影响因子：
5.6
通讯作者：
Yan，Guanghai
中科院分区：
文献类型：
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作者：
Wang，Chongyang;Zheng，Mingyu;Yan，Guanghai
本研究旨在探讨隐丹参酮（CTS）对气道重塑的影响及其可能机制。雄性BALB/c小鼠在雾化吸入卵清蛋白（OVA）前30 min用CTS或地塞米松预处理。CTS能显著抑制OVA诱导的支气管肺泡灌洗液（BALF）中嗜酸性粒细胞和中性粒细胞浸润，降低哮喘小鼠气道阻力，减少哮喘小鼠肺组织中炎性细胞的积聚、杯状细胞的增生和胶原的沉积，并能显著减少BALF中炎性细胞的漏出和OVA特异性免疫球蛋白E的水平。CTS还抑制α-平滑肌肌动蛋白、肿瘤坏死因子样弱凋亡诱导因子（TWEAK）、Fn 14、转化生长因子（TGF）-β1、Smad 4的表达以及Smad 2/3和STAT 3（Tyr 705）的磷酸化。与用于抑制TWEAK/STAT 3信号通路的TWEAK抑制剂或TWEAK小干扰RNA（siRNA）相比，CTS对气道重塑的影响与它们相似。此外，CTS在气道重塑过程中也发挥了与TGF-β1抑制剂或TGF-β1 siRNA类似的作用。CTS的抗炎作用可能是通过抑制STAT 3，进而抑制哮喘中TWEAK和TGF-β1信号通路的相互作用。CTS可能是一种很有前途的治疗哮喘的药物。
The study is to investigate the effect of cryptotanshinone (CTS) on airway remodeling and the possible mechanism. Male BALB/c mice were pretreated with CTS or dexamethasone 30 min before nebulized inhalation of ovalbumin (OVA). CTS significantly inhibited OVA-induced increases of eosinophils and neutrophils infiltration of bronchoalveolar lavage fluids (BALFs), reduced airway resistance in asthmatic mice, decreased the accumulation of inflammatory cells, the hyperplasia of goblet cells and the deposition of collagen in asthmatic mice lung tissue, as well as markedly attenuated the leakage of inflammatory cells and the level of OVA-specific immunoglobulin E in BALFs. CTS also inhibited the expressions of alpha-smooth muscle actin, tumor necrosis factor-like weak inducer of apoptosis (TWEAK), Fn14, transforming growth factor (TGF)-β1, Smad4, and phosphorylation of Smad2/3 and STAT3 (Tyr705). In comparison to TWEAK inhibitor or TWEAK small interfering RNA (siRNA), which were used to inhibit TWEAK/STAT3 signaling pathways, CTS caused a similar effect as them on airway remodeling. Additionally, CTS also played a similar role as the TGF-β1 inhibitor or TGF-β1 siRNA in TGF-β1/STAT3 signaling pathways in airway remodeling. The anti-inflammatory effects of CTS against OVA-induced airway remodeling may be through inhibiting STAT3, which further suppresses TWEAK and TGF-β1 signaling cross talk in asthma. CTS may be a promising therapeutic reagent for asthma treatment.