Suberoylanilide hydroxamic acid attenuates paraquat-induced pulmonary fibrosis by preventing Smad7 from deacetylation in rats
Suberoylanilide hydroxamic acid attenuates paraquat-induced pulmonary fibrosis by preventing Smad7 from deacetylation in rats
复制标题
辛二酰苯胺异羟肟酸通过阻止 Smad7 脱乙酰化来减轻百草枯诱导的大鼠肺纤维化
DOI：
10.21037/jtd.2016.08.08
复制
发表时间：
2016-09-01
影响因子：
2.5
通讯作者：
Guo, Bing
中科院分区：
文献类型：
--
作者：
Rao, Shan-Shan;Zhang, Xiang-Yan;Guo, Bing
背景：最近的证据表明，组蛋白脱乙酰酶抑制剂--异羟肟酸(SAHA)具有抗肝纤维化的作用。然而，其抗纤维化作用的确切机制尚不清楚。本研究通过调节Smad7在百草枯(PQ)诱导的肺纤维化动物模型和培养的肺成纤维细胞中的稳定性，探讨SAHA抗肺纤维化的分子机制。结果：SAHA(组蛋白去乙酰酶抑制剂，HDACi)通过稳定Smad7水平抑制PQ诱导的大鼠肺纤维化，从而抑制Smad3活性，从而抑制成纤维细胞分化和胶原蛋白表达。体外研究表明，SAHA抑制了转化生长因子-β1诱导的成纤维细胞向肌成纤维细胞的分化。SAHA通过阻止Smad7脱乙酰化发挥抗纤维化作用，可能主要是通过抑制转化生长因子-β1诱导的HDAC1活性发挥作用。结论：SAHA通过阻止Smad7脱乙酰化抑制PQ诱导的肺纤维化。
Background: Recent evidence suggests that a histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), has anti-fibrotic effect. However, the exact mechanism of its anti-fibrotic potential remains is unclear. In this study, we investigated the molecular mechanism of SAHA in attenuating pulmonary fibrosis by regulating stability of Smad7 in paraquat (PQ)-induced lung fibrosis animal model and cultured pulmonary fibroblasts.Methods: Rats with paraquat-induced lung fibrosis were fed with a SAHA solution (15 mg/kg) by gastric gavage. Human pulmonary fibroblasts (HFL1) pre-treated with TGF-beta 1 (5 ng/mL) were treated with SAHA (5 mu M).Results: SAHA (histone deacetylase inhibitor, HDACi) suppressed PQ-induced lung fibrosis in rats by stabilizing Smad7 level, thus attenuating Smad3 activity, resulting in the inhibition of fibroblast differentiation and collagen expression. In vitro study showed that SAHA suppressed TGF-beta 1-induced fibroblast differentiation into myofibroblasts. SAHA exerted its antifibrotic effect through preventing Smad7 from deacetylation most maybe by inhibiting TGF-beta 1-induced HDAC1 activity.Conclusions: SAHA repressed PQ-induced lung fibrosis via preventing Smad7 from deacetylation.