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.

journal_name

J Thorac Dis

authors

Rao SS,Zhang XY,Shi MJ,Xiao Y,Zhang YY,Wang YY,Zhang CZ,Shao SJ,Liu XM,Guo B

doi

10.21037/jtd.2016.08.08

subject

Has Abstract

pub_date

2016-09-01 00:00:00

pages

2485-2494

issue

9

eissn

2072-1439

issn

2077-6624

pii

jtd-08-09-2485

journal_volume

8

pub_type

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