Niclosamide alleviates pulmonary fibrosis in vitro and in vivo by attenuation of epithelial-to-mesenchymal transition, matrix proteins & Wnt/β-catenin signaling: A drug repurposing study
Niclosamide alleviates pulmonary fibrosis in vitro and in vivo by attenuation of epithelial-to-mesenchymal transition, matrix proteins & Wnt/β-catenin signaling: A drug repurposing study
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DOI：
10.1016/j.lfs.2018.12.061
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发表时间：
2019-03-01
期刊：
影响因子：
6.1
通讯作者：
Godugu, Chandraiah
中科院分区：
文献类型：
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作者：
Boyapally, Raju;Pulivendala, Gauthami;Godugu, Chandraiah
药物再利用已经成为一种鼓舞人心的替代方法，传统的，详尽的和艰苦的药物发现过程。它是一个为已经确定用于治疗某种疾病的药物确定新的治疗价值的过程。我们目前的研究旨在将旧的抗幽门螺杆菌药物氯硝柳胺重新利用为抗肺纤维化（PF）的抗纤维化药物。PF是最常见的致死性间质性肺疾病，以肺细胞外基质沉积和瘢痕形成为特征。肺纤维化的异质性、不及时的诊断和缺乏适当的治疗选择使得肺纤维化成为一种不可避免的肺部疾病。PF治疗和药物重新定位策略中的普遍空白点燃了我们证明氯硝柳胺抗纤维化活性的兴趣。本研究旨在探讨氯硝柳胺对TGF-β 1诱导的PF体外模型和博来霉素诱导的PF 21天体内模型的抗纤维化作用。我们的研究结果表明，氯硝柳胺具有通过阻碍成纤维细胞迁移、减弱EMT、抑制纤维化信号传导和通过调节WNT/β-连环蛋白信号传导发挥抗纤维化作用的潜力，如蛋白质表达研究所证实的。本研究结果为氯硝柳胺作为抗肺纤维化药物的开发提供了新的方向。
Drug repurposing off late has been emerging as an inspiring alternative approach to conventional, exhaustive and arduous process of drug discovery. It is a process of identifying new therapeutic values for a drug already established for the treatment of a certain condition. Our current study is aimed at repurposing the old anti-helimenthic drug Niclosamide as an anti-fibrotic drug against pulmonary fibrosis (PF). PF is most common lethal interstitial lung disease hallmarked by deposition of extracelluar matrix and scarring of lung. Heterogenous nature, untimely diagnosis and lack of appropriate treatment options make PF an inexorable lung disorder. Prevailing void in PF treatment and drug repositioning strategy of drugs kindled our interest to demonstrate the anti-fibrotic activity of Niclosamide. Our study is aimed at investigating the anti-fibrotic potential of Niclosamide in TGF-beta 1 induced in vitro model of PF and 21-day model of Bleomycin induced PF in vivo respectively. Our study results showed that Niclosamide holds the potential to exert anti-fibrotic effect by hampering fibroblast migration, attenuating EMT, inhibiting fibrotic signaling and by regulating WNT/beta-catenin signaling as evident from protein expression studies. Our study findings can give new directions to development of Niclosamide as an anti-fibrotic agent for treatment of pulmonary fibrosis.