Characterization of transcriptional modules related to fibrosing-NAFLD progression

Abstract Based on the severity of liver fibrosis, low or high-risk profile of developing end-stage liver disease was present in nonalcoholic fatty liver disease (NAFLD). However, the mechanisms inducing transition from mild to advanced NAFLD are still elusive. We performed a system-level study on fi...

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Autores principales:	Yi Lou, Guo-Yan Tian, Yu Song, Yin-Lan Liu, Yi-Dan Chen, Jun-Ping Shi, Jin Yang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f9af26ac50d24f17b8280968da486ed9
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spelling	oai:doaj.org-article:f9af26ac50d24f17b8280968da486ed92021-12-02T15:05:38ZCharacterization of transcriptional modules related to fibrosing-NAFLD progression10.1038/s41598-017-05044-22045-2322https://doaj.org/article/f9af26ac50d24f17b8280968da486ed92017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05044-2https://doaj.org/toc/2045-2322Abstract Based on the severity of liver fibrosis, low or high-risk profile of developing end-stage liver disease was present in nonalcoholic fatty liver disease (NAFLD). However, the mechanisms inducing transition from mild to advanced NAFLD are still elusive. We performed a system-level study on fibrosing-NAFLD by weighted gene co-expression network analysis (WGCNA) to identify significant modules in the network, and followed by functional and pathway enrichment analyses. Moreover, hub genes in the module were analyzed by network feature selection. As a result, fourteen distinct gene modules were identified, and seven modules showed significant associations with the status of NAFLD. Module preservation analysis confirmed that these modules can also be found in diverse independent datasets. After network feature analysis, the magenta module demonstrated a remarkably correlation with NAFLD fibrosis. The top hub genes with high connectivity or gene significance in the module were ultimately determined, including LUM, THBS2, FBN1 and EFEMP1. These genes were further verified in clinical samples. Finally, the potential regulators of magenta module were characterized. These findings highlighted a module and affiliated genes as playing important roles in the regulation of fibrosis in NAFLD, which may point to potential targets for therapeutic interventions.Yi LouGuo-Yan TianYu SongYin-Lan LiuYi-Dan ChenJun-Ping ShiJin YangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yi Lou Guo-Yan Tian Yu Song Yin-Lan Liu Yi-Dan Chen Jun-Ping Shi Jin Yang Characterization of transcriptional modules related to fibrosing-NAFLD progression
description	Abstract Based on the severity of liver fibrosis, low or high-risk profile of developing end-stage liver disease was present in nonalcoholic fatty liver disease (NAFLD). However, the mechanisms inducing transition from mild to advanced NAFLD are still elusive. We performed a system-level study on fibrosing-NAFLD by weighted gene co-expression network analysis (WGCNA) to identify significant modules in the network, and followed by functional and pathway enrichment analyses. Moreover, hub genes in the module were analyzed by network feature selection. As a result, fourteen distinct gene modules were identified, and seven modules showed significant associations with the status of NAFLD. Module preservation analysis confirmed that these modules can also be found in diverse independent datasets. After network feature analysis, the magenta module demonstrated a remarkably correlation with NAFLD fibrosis. The top hub genes with high connectivity or gene significance in the module were ultimately determined, including LUM, THBS2, FBN1 and EFEMP1. These genes were further verified in clinical samples. Finally, the potential regulators of magenta module were characterized. These findings highlighted a module and affiliated genes as playing important roles in the regulation of fibrosis in NAFLD, which may point to potential targets for therapeutic interventions.
format	article
author	Yi Lou Guo-Yan Tian Yu Song Yin-Lan Liu Yi-Dan Chen Jun-Ping Shi Jin Yang
author_facet	Yi Lou Guo-Yan Tian Yu Song Yin-Lan Liu Yi-Dan Chen Jun-Ping Shi Jin Yang
author_sort	Yi Lou
title	Characterization of transcriptional modules related to fibrosing-NAFLD progression
title_short	Characterization of transcriptional modules related to fibrosing-NAFLD progression
title_full	Characterization of transcriptional modules related to fibrosing-NAFLD progression
title_fullStr	Characterization of transcriptional modules related to fibrosing-NAFLD progression
title_full_unstemmed	Characterization of transcriptional modules related to fibrosing-NAFLD progression
title_sort	characterization of transcriptional modules related to fibrosing-nafld progression
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f9af26ac50d24f17b8280968da486ed9
work_keys_str_mv	AT yilou characterizationoftranscriptionalmodulesrelatedtofibrosingnafldprogression AT guoyantian characterizationoftranscriptionalmodulesrelatedtofibrosingnafldprogression AT yusong characterizationoftranscriptionalmodulesrelatedtofibrosingnafldprogression AT yinlanliu characterizationoftranscriptionalmodulesrelatedtofibrosingnafldprogression AT yidanchen characterizationoftranscriptionalmodulesrelatedtofibrosingnafldprogression AT junpingshi characterizationoftranscriptionalmodulesrelatedtofibrosingnafldprogression AT jinyang characterizationoftranscriptionalmodulesrelatedtofibrosingnafldprogression
_version_	1718388806800900096

Characterization of transcriptional modules related to fibrosing-NAFLD progression

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