Gene expression profiling and network analysis reveals lipid and steroid metabolism to be the most favored by TNFalpha in HepG2 cells.

<h4>Background</h4>The proinflammatory cytokine, TNFalpha, is a crucial mediator of the pathogenesis of several diseases, more so in cases involving the liver wherein it is critical in maintaining liver homeostasis since it is a major determiner of hepatocyte life and death. Gene express...

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Autores principales:	Amit K Pandey, Neha Munjal, Malabika Datta
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/31d83fcf27ff4e5ebc311ab0e8a77e82
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spelling	oai:doaj.org-article:31d83fcf27ff4e5ebc311ab0e8a77e822021-11-25T06:26:07ZGene expression profiling and network analysis reveals lipid and steroid metabolism to be the most favored by TNFalpha in HepG2 cells.1932-620310.1371/journal.pone.0009063https://doaj.org/article/31d83fcf27ff4e5ebc311ab0e8a77e822010-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20140224/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The proinflammatory cytokine, TNFalpha, is a crucial mediator of the pathogenesis of several diseases, more so in cases involving the liver wherein it is critical in maintaining liver homeostasis since it is a major determiner of hepatocyte life and death. Gene expression profiling serves as an appropriate strategy to unravel the underlying signatures to envisage such varied responses and considering this, gene transcription profiling was examined in control and TNFalpha treated HepG2 cells.<h4>Methods and findings</h4>Microarray experiments between control and TNFalpha treated HepG2 cells indicated that TNFalpha could significantly alter the expression profiling of 140 genes; among those up-regulated, several GO (Gene Ontology) terms related to lipid and fat metabolism were significantly (p<0.01) overrepresented indicating a global preference of fat metabolism within the hepatocyte and those within the down-regulated dataset included genes involved in several aspects of the immune response like immunoglobulin receptor activity and IgE binding thereby indicating a compromise in the immune defense mechanism(s). Conserved transcription factor binding sites were identified in identically clustered genes within a common GO term and SREBP-1 and FOXJ2 depicted increased occupation of their respective binding elements in the presence of TNFalpha. The interacting network of "lipid metabolism, small molecule biochemistry" was derived to be significantly overrepresented that correlated well with the top canonical pathway of "biosynthesis of steroids".<h4>Conclusions</h4>TNFalpha alters the transcriptome profiling within HepG2 cells with an interesting catalog of genes being affected and those involved in lipid and steroid metabolism to be the most favored. This study represents a composite analysis of the effects of TNFalpha in HepG2 cells that encompasses the altered transcriptome profiling, the functional analysis of the up- and down- regulated genes and the identification of conserved transcription factor binding sites. These could possibly determine TNFalpha mediated alterations mainly the phenotypes of hepatic steatosis and fatty liver associated with several hepatic pathological states.Amit K PandeyNeha MunjalMalabika DattaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 2, p e9063 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Amit K Pandey Neha Munjal Malabika Datta Gene expression profiling and network analysis reveals lipid and steroid metabolism to be the most favored by TNFalpha in HepG2 cells.
description	<h4>Background</h4>The proinflammatory cytokine, TNFalpha, is a crucial mediator of the pathogenesis of several diseases, more so in cases involving the liver wherein it is critical in maintaining liver homeostasis since it is a major determiner of hepatocyte life and death. Gene expression profiling serves as an appropriate strategy to unravel the underlying signatures to envisage such varied responses and considering this, gene transcription profiling was examined in control and TNFalpha treated HepG2 cells.<h4>Methods and findings</h4>Microarray experiments between control and TNFalpha treated HepG2 cells indicated that TNFalpha could significantly alter the expression profiling of 140 genes; among those up-regulated, several GO (Gene Ontology) terms related to lipid and fat metabolism were significantly (p<0.01) overrepresented indicating a global preference of fat metabolism within the hepatocyte and those within the down-regulated dataset included genes involved in several aspects of the immune response like immunoglobulin receptor activity and IgE binding thereby indicating a compromise in the immune defense mechanism(s). Conserved transcription factor binding sites were identified in identically clustered genes within a common GO term and SREBP-1 and FOXJ2 depicted increased occupation of their respective binding elements in the presence of TNFalpha. The interacting network of "lipid metabolism, small molecule biochemistry" was derived to be significantly overrepresented that correlated well with the top canonical pathway of "biosynthesis of steroids".<h4>Conclusions</h4>TNFalpha alters the transcriptome profiling within HepG2 cells with an interesting catalog of genes being affected and those involved in lipid and steroid metabolism to be the most favored. This study represents a composite analysis of the effects of TNFalpha in HepG2 cells that encompasses the altered transcriptome profiling, the functional analysis of the up- and down- regulated genes and the identification of conserved transcription factor binding sites. These could possibly determine TNFalpha mediated alterations mainly the phenotypes of hepatic steatosis and fatty liver associated with several hepatic pathological states.
format	article
author	Amit K Pandey Neha Munjal Malabika Datta
author_facet	Amit K Pandey Neha Munjal Malabika Datta
author_sort	Amit K Pandey
title	Gene expression profiling and network analysis reveals lipid and steroid metabolism to be the most favored by TNFalpha in HepG2 cells.
title_short	Gene expression profiling and network analysis reveals lipid and steroid metabolism to be the most favored by TNFalpha in HepG2 cells.
title_full	Gene expression profiling and network analysis reveals lipid and steroid metabolism to be the most favored by TNFalpha in HepG2 cells.
title_fullStr	Gene expression profiling and network analysis reveals lipid and steroid metabolism to be the most favored by TNFalpha in HepG2 cells.
title_full_unstemmed	Gene expression profiling and network analysis reveals lipid and steroid metabolism to be the most favored by TNFalpha in HepG2 cells.
title_sort	gene expression profiling and network analysis reveals lipid and steroid metabolism to be the most favored by tnfalpha in hepg2 cells.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/31d83fcf27ff4e5ebc311ab0e8a77e82
work_keys_str_mv	AT amitkpandey geneexpressionprofilingandnetworkanalysisrevealslipidandsteroidmetabolismtobethemostfavoredbytnfalphainhepg2cells AT nehamunjal geneexpressionprofilingandnetworkanalysisrevealslipidandsteroidmetabolismtobethemostfavoredbytnfalphainhepg2cells AT malabikadatta geneexpressionprofilingandnetworkanalysisrevealslipidandsteroidmetabolismtobethemostfavoredbytnfalphainhepg2cells
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Gene expression profiling and network analysis reveals lipid and steroid metabolism to be the most favored by TNFalpha in HepG2 cells.

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