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Int. J. Mol. Sci. 2013, 14(10), 19605-19617; doi:10.3390/ijms141019605
Article

Histone Deacetylase Inhibition Downregulates Collagen 3A1 in Fibrotic Lung Fibroblasts

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Received: 8 July 2013; in revised form: 27 August 2013 / Accepted: 11 September 2013 / Published: 27 September 2013
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Abstract: Idiopathic pulmonary fibrosis (IPF) is a deadly disease characterized by chronic inflammation and excessive collagen accumulation in the lung. Myofibroblasts are the primary collagen-producing cells in pulmonary fibrosis. Histone deacetylase inhibitor (HDACi) can affect gene expression, and some, such as suberoylanilide hydroxamic acid (SAHA), are US FDA approved for cancer treatment. In this study, we investigated SAHA’s effects on the expression of collagen III alpha 1 (COL3A1) in primary human IPF fibroblasts and in a murine model of pulmonary fibrosis. We observed that increased COL3A1 expression in IPF fibroblasts can be substantially reduced by SAHA treatment at the level of transcription as detected by RT-PCR; collagen III protein level was also reduced, as detected by Western blots and immunofluorescence. The deacetylation inhibitor effect of SAHA was verified by observing higher acetylation levels of both histone H3 and H4 in treated IPF cells. Chromatin immunoprecipitation (ChIP) experiments demonstrated that the reduced expression of COL3A1 by SAHA is with increased association of the repressive chromatin marker, H3K27Me3, and decreased association of the active chromatin marker, H3K9Ac. In our murine model of bleomycin-induced pulmonary fibrosis, the SAHA treated group demonstrated significantly less collagen III, as detected by immunohistochemistry. Our data indicate that the HDACi SAHA alters the chromatin associated with COL3A1, resulting in its decreased expression.
Keywords: histone deacetylase inhibitor (HDACi); suberoylanilide hydroxamic acid (SAHA); histone modification; epigenetic; collagen III; COL3A1; fibroblasts; idiopathic pulmonary fibrosis (IPF) histone deacetylase inhibitor (HDACi); suberoylanilide hydroxamic acid (SAHA); histone modification; epigenetic; collagen III; COL3A1; fibroblasts; idiopathic pulmonary fibrosis (IPF)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Zhang, X.; Liu, H.; Hock, T.; Thannickal, V.J.; Sanders, Y.Y. Histone Deacetylase Inhibition Downregulates Collagen 3A1 in Fibrotic Lung Fibroblasts. Int. J. Mol. Sci. 2013, 14, 19605-19617.

AMA Style

Zhang X, Liu H, Hock T, Thannickal VJ, Sanders YY. Histone Deacetylase Inhibition Downregulates Collagen 3A1 in Fibrotic Lung Fibroblasts. International Journal of Molecular Sciences. 2013; 14(10):19605-19617.

Chicago/Turabian Style

Zhang, Xiangyu; Liu, Hui; Hock, Thomas; Thannickal, Victor J.; Sanders, Yan Y. 2013. "Histone Deacetylase Inhibition Downregulates Collagen 3A1 in Fibrotic Lung Fibroblasts." Int. J. Mol. Sci. 14, no. 10: 19605-19617.



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