Lipopolysaccharide induces up-regulation of TGF-α through HDAC2 in a rat model of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is characterized by alveolar simplification with decreased alveolar number and increased airspace. Previous studies suggested that transforming growth factor-α (TGF-α) may contribute to arrested alveolar development in BPD. Histone deacetylases (HDACs) control cellul...

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Autores principales:	Wensi Ni, Ning Lin, Hua He, Jianxing Zhu, Yongjun Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b14c010fd98e4c20942a9efd331d23af
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spelling	oai:doaj.org-article:b14c010fd98e4c20942a9efd331d23af2021-11-18T08:29:46ZLipopolysaccharide induces up-regulation of TGF-α through HDAC2 in a rat model of bronchopulmonary dysplasia.1932-620310.1371/journal.pone.0091083https://doaj.org/article/b14c010fd98e4c20942a9efd331d23af2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24595367/?tool=EBIhttps://doaj.org/toc/1932-6203Bronchopulmonary dysplasia (BPD) is characterized by alveolar simplification with decreased alveolar number and increased airspace. Previous studies suggested that transforming growth factor-α (TGF-α) may contribute to arrested alveolar development in BPD. Histone deacetylases (HDACs) control cellular signaling and gene expression. HDAC2 is crucial for suppression of inflammatory gene expression. Here we investigated whether HDAC2 was involved in the arrest of alveolarization, as well as the ability of HDAC2 to regulate TGF-α expression in a rat model of BPD induced by intra-amniotic injection of lipopolysaccharide (LPS). Results showed that LPS exposure led to a suppression of both HDAC1 and HDAC2 expression and activity, induced TGF-α expression, and disrupted alveolar morphology. Mechanistic studies showed that overexpression of HDAC2, but not HDAC1, suppressed LPS-induced TGF-α expression. Moreover, the HDAC inhibitor TSA or downregulation of HDAC2 by siRNA both significantly increased TGF-α expression in cultured myofibroblasts. Finally, preservation of HDAC activity by theophylline treatment improved alveolar development and attenuated TGF-α release. Together, these findings indicate that attenuation of TGF-α-mediated effects in the lung by enhancing HDAC2 may have a therapeutic effect on treating BPD.Wensi NiNing LinHua HeJianxing ZhuYongjun ZhangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 3, p e91083 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wensi Ni Ning Lin Hua He Jianxing Zhu Yongjun Zhang Lipopolysaccharide induces up-regulation of TGF-α through HDAC2 in a rat model of bronchopulmonary dysplasia.
description	Bronchopulmonary dysplasia (BPD) is characterized by alveolar simplification with decreased alveolar number and increased airspace. Previous studies suggested that transforming growth factor-α (TGF-α) may contribute to arrested alveolar development in BPD. Histone deacetylases (HDACs) control cellular signaling and gene expression. HDAC2 is crucial for suppression of inflammatory gene expression. Here we investigated whether HDAC2 was involved in the arrest of alveolarization, as well as the ability of HDAC2 to regulate TGF-α expression in a rat model of BPD induced by intra-amniotic injection of lipopolysaccharide (LPS). Results showed that LPS exposure led to a suppression of both HDAC1 and HDAC2 expression and activity, induced TGF-α expression, and disrupted alveolar morphology. Mechanistic studies showed that overexpression of HDAC2, but not HDAC1, suppressed LPS-induced TGF-α expression. Moreover, the HDAC inhibitor TSA or downregulation of HDAC2 by siRNA both significantly increased TGF-α expression in cultured myofibroblasts. Finally, preservation of HDAC activity by theophylline treatment improved alveolar development and attenuated TGF-α release. Together, these findings indicate that attenuation of TGF-α-mediated effects in the lung by enhancing HDAC2 may have a therapeutic effect on treating BPD.
format	article
author	Wensi Ni Ning Lin Hua He Jianxing Zhu Yongjun Zhang
author_facet	Wensi Ni Ning Lin Hua He Jianxing Zhu Yongjun Zhang
author_sort	Wensi Ni
title	Lipopolysaccharide induces up-regulation of TGF-α through HDAC2 in a rat model of bronchopulmonary dysplasia.
title_short	Lipopolysaccharide induces up-regulation of TGF-α through HDAC2 in a rat model of bronchopulmonary dysplasia.
title_full	Lipopolysaccharide induces up-regulation of TGF-α through HDAC2 in a rat model of bronchopulmonary dysplasia.
title_fullStr	Lipopolysaccharide induces up-regulation of TGF-α through HDAC2 in a rat model of bronchopulmonary dysplasia.
title_full_unstemmed	Lipopolysaccharide induces up-regulation of TGF-α through HDAC2 in a rat model of bronchopulmonary dysplasia.
title_sort	lipopolysaccharide induces up-regulation of tgf-α through hdac2 in a rat model of bronchopulmonary dysplasia.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/b14c010fd98e4c20942a9efd331d23af
work_keys_str_mv	AT wensini lipopolysaccharideinducesupregulationoftgfathroughhdac2inaratmodelofbronchopulmonarydysplasia AT ninglin lipopolysaccharideinducesupregulationoftgfathroughhdac2inaratmodelofbronchopulmonarydysplasia AT huahe lipopolysaccharideinducesupregulationoftgfathroughhdac2inaratmodelofbronchopulmonarydysplasia AT jianxingzhu lipopolysaccharideinducesupregulationoftgfathroughhdac2inaratmodelofbronchopulmonarydysplasia AT yongjunzhang lipopolysaccharideinducesupregulationoftgfathroughhdac2inaratmodelofbronchopulmonarydysplasia
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Lipopolysaccharide induces up-regulation of TGF-α through HDAC2 in a rat model of bronchopulmonary dysplasia.

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