Department of Internal Medicine, Institute of Wonkwang Medical Science, Wonkwang University, School of Medicine, Iksan, Jeonbuk 54538, Korea.
Medical Convergence Research Center, Wonkwang University Hospital, Iksan, Jeonbuk 54538, Korea.
Molecules. 2019 Jul 31;24(15):2792. doi: 10.3390/molecules24152792.
Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with poor prognosis and progression to lung fibrosis related to genetic factors as well as environmental factors. In fact, it was discovered that in South Korea many people who used humidifier disinfectants containing polyhexamethylene guanidine (PHMG), died of lung fibrosis. Currently two anti-fibrotic drugs, pirfenidone and nintedanib, have been approved by the FDA, but unfortunately, do not cure the disease. Since the histone deacetylase (HDAC) activity is associated with progression to chronic diseases and with fibrotic phenomena in the kidney, heart and lung tissues, we investigated the anti-fibrotic effects of CG-745, an HDAC inhibitor. After lung fibrosis was induced in two animal models by bleomycin and PHMG instillation, the regulation of fibrosis and epithelial mesenchymal transition (EMT)-related markers was assessed. CG-745 exhibited potent prevention of collagen production, inflammatory cell accumulation, and cytokines release in both models. Additionally, N-cadherin and vimentin expression were lowered significantly by the treatment of CG-745. The anti-fibrotic effects of CG-745 proven by the EMT regulation may suggest a potential therapeutic effect of CG-745 on lung fibrosis.
特发性肺纤维化（IPF）是一种致命的肺部疾病，预后不良，与遗传因素和环境因素有关的肺纤维化进展。事实上，人们发现韩国许多使用含有聚六亚甲基胍（PHMG）的加湿器消毒剂的人死于肺纤维化。目前，两种抗纤维化药物——吡非尼酮和尼达尼布已被 FDA 批准，但不幸的是，它们并不能治愈这种疾病。由于组蛋白去乙酰化酶（HDAC）活性与慢性疾病的进展以及肾脏、心脏和肺组织中的纤维化现象有关，我们研究了 HDAC 抑制剂 CG-745 的抗纤维化作用。在博来霉素和 PHMG 滴注诱导两种动物模型发生肺纤维化后，评估了纤维化和上皮间质转化（EMT）相关标志物的调节。CG-745 在两种模型中均表现出对胶原产生、炎症细胞积聚和细胞因子释放的强烈预防作用。此外，CG-745 治疗还显著降低了 N-钙黏蛋白和波形蛋白的表达。CG-745 通过调节 EMT 显示出的抗纤维化作用可能提示 CG-745 对肺纤维化具有潜在的治疗作用。
