title: Suberoylanilide hydroxamic acid attenuates paraquat-induced pulmonary fibrosis by preventing Smad7 from deacetylation in rats.
abstract: 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-β1 (5 ng/mL) were treated with SAHA (5 µM).
  
  
  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-β1-induced fibroblast differentiation into myofibroblasts. SAHA exerted its antifibrotic effect through preventing Smad7 from deacetylation most maybe by inhibiting TGF-β1-induced HDAC1 activity.
  
  
  CONCLUSIONS
  SAHA repressed PQ-induced lung fibrosis via preventing Smad7 from deacetylation.
authors.affiliation: Department of Pathophysiology, Guizhou Medical University, Guiyang 550025, China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Rao
authors.affiliation: Department of Respiratory Medicine, The People's Hospital of Guizhou Province, Guiyang 550025, China;; Academic Department, Guizhou Institute of Respiratory Diseases, Guiyang 55002, China.
authors.forename: Xiang-Yan
authors.initials: XY
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Guizhou Medical University, Guiyang 550025, China.
authors.forename: Ming-Jun
authors.initials: MJ
authors.lastname: Shi
authors.affiliation: Department of Pathophysiology, Guizhou Medical University, Guiyang 550025, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Pathophysiology, Guizhou Medical University, Guiyang 550025, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Guizhou Medical University, Guiyang 550025, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Guizhou Medical University, Guiyang 550025, China.
authors.forename: Chang-Zhi
authors.initials: CZ
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Guizhou Medical University, Guiyang 550025, China.
authors.forename: Song-Jun
authors.initials: SJ
authors.lastname: Shao
authors.affiliation: Department of Pathophysiology, Guizhou Medical University, Guiyang 550025, China.
authors.forename: Xin-Mei
authors.initials: XM
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Guizhou Medical University, Guiyang 550025, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Guo
keywords: Pulmonary fibrosis; Smad7 acetylation; TGF-β1; histone deacetylase 1 (HDAC1); suberoylanilide hydroxamic acid (SAHA)