Histone deacetylase inhibitor restores surfactant protein-C expression in alveolar-epithelial type II cells and attenuates bleomycin-induced pulmonary fibrosis in vivo.

ABSTRACTAim: Surfactant protein-C (SP-C) of alveolar epithelial type II cells (ATII) plays a key role in maintaining alveolar integrity and repair. Mutations or decreased expression of SFTPC, the gene encoding SP-C, causes ATII injury and aberrant repair of the lung tissue to develop pulmonary fibrosis. Histone deacetylases (HDACs) epigenetically remove acetyl groups from acetylated histones and regulate transcription. HDAC inhibitors attenuated epithelial-to-mesenchymal transition (EMT) and fibrotic disorders. The aim of this study is to investigate whether Trichostatin A (TSA), a pan-HDAC inhibitor, epigenetically exerts a protective effect on ATII against fibrotic changes via the restoration of SFTPC expression. Materials and Methods: We treated A549 cells with TGF-β1 to induce EMT, followed by TSA treatment. We evaluated SFTPC mRNA, histone acetylation levels in the SFTPC gene promoter region, and pro-SP-C protein. C57BL6/J mice were treated with intratracheal bleomycin instillation followed by TSA ad...