Kim Sung-Ho, Pei Qing-Mei, Jiang Ping, Yang Min, Qian Xue-Jiao, Liu Jiang-Bo
a Department of Respiration , Tianjin First Central Hospital , Tianjin , P.R. China and.
b Department of Radiology , Tianjin Hospital of Integrated Traditional Chinese and Western Medicine , Tianjin , P.R. China.
Growth Factors. 2017 Feb;35(1):39-47. doi: 10.1080/08977194.2017.1338694.
Asthma is a chronic respiratory disease characterized by reversible airway obstruction with persistent airway inflammation and airway remodeling, which is associated with increased airway smooth muscle (ASM) mass. Licochalcone A is the predominant characteristic chalcone in licorice root. We found that licochalcone A inhibited vascular endothelial growth factor (VEGF)-induced ASM cell proliferation and induced cell cycle arrest. Additionally, VEGF-induced ASM cell proliferation was suppressed via inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) activity, but not that of Akt. Furthermore, licochalcone A treatment inhibited VEGF-induced activation of VEGF receptor 2 (VEGFR2) and ERK and blocked the downregulation of caveolin-1 in a concentration-dependent manner. Collectively, our findings suggested that licochalcone A inhibited VEGF-induced ASM cell proliferation by suppressing VEGFR2 and ERK1/2 activation and downregulating caveolin-1. Further studies of these mechanisms are needed to facilitate the development of treatments for smooth muscle hyperplasia-associated diseases of the airway, such as asthma.
哮喘是一种慢性呼吸道疾病,其特征为可逆性气道阻塞,并伴有持续性气道炎症和气道重塑,这与气道平滑肌(ASM)质量增加有关。甘草查尔酮A是甘草根中的主要特征性查尔酮。我们发现甘草查尔酮A可抑制血管内皮生长因子(VEGF)诱导的ASM细胞增殖,并诱导细胞周期停滞。此外,VEGF诱导的ASM细胞增殖通过抑制细胞外信号调节激酶1/2(ERK1/2)活性而受到抑制,但Akt活性不受抑制。此外,甘草查尔酮A处理以浓度依赖的方式抑制VEGF诱导的VEGF受体2(VEGFR2)和ERK激活,并阻断小窝蛋白-1的下调。总体而言,我们的研究结果表明,甘草查尔酮A通过抑制VEGFR2和ERK1/2激活以及下调小窝蛋白-1来抑制VEGF诱导的ASM细胞增殖。需要对这些机制进行进一步研究,以促进针对气道平滑肌增生相关疾病(如哮喘)的治疗方法的开发。