cAMP response element binding protein1 is essential for activation of steroyl co-enzyme a desaturase 1 (Scd1) in mouse lung type II epithelial cells.

Cyclic AMP Response Element-Binding Protein 1 (Creb1) is a transcription factor that mediates cyclic adenosine 3', 5'-monophosphate (cAMP) signalling in many tissues. Creb1(-/-) mice die at birth due to respiratory failure and previous genome-wide microarray analysis of E17.5 Creb1(-/-) fe...

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Autores principales:	Nisha Antony, Jacqui R Weir, Annie R A McDougall, Theo Mantamadiotis, Peter J Meikle, Timothy J Cole, Anthony D Bird
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/95d05cfa6f7d42fd94fc268b0a632424
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spelling	oai:doaj.org-article:95d05cfa6f7d42fd94fc268b0a6324242021-11-18T07:48:56ZcAMP response element binding protein1 is essential for activation of steroyl co-enzyme a desaturase 1 (Scd1) in mouse lung type II epithelial cells.1932-620310.1371/journal.pone.0059763https://doaj.org/article/95d05cfa6f7d42fd94fc268b0a6324242013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23637738/?tool=EBIhttps://doaj.org/toc/1932-6203Cyclic AMP Response Element-Binding Protein 1 (Creb1) is a transcription factor that mediates cyclic adenosine 3', 5'-monophosphate (cAMP) signalling in many tissues. Creb1(-/-) mice die at birth due to respiratory failure and previous genome-wide microarray analysis of E17.5 Creb1(-/-) fetal mouse lung identified important Creb1-regulated gene targets during lung development. The lipogenic enzymes stearoyl-CoA desaturase 1 (Scd1) and fatty acid synthase (Fasn) showed highly reduced gene expression in Creb1(-/-) lungs. We therefore hypothesized that Creb1 plays a crucial role in the transcriptional regulation of genes involved in pulmonary lipid biosynthetic pathways during lung development. In this study we confirmed that Scd1 and Fasn mRNA levels were down regulated in the E17.5 Creb1(-/-) mouse lung while the lipogenic-associated transcription factors SrebpF1, C/ebpα and Pparγ were increased. In vivo studies using germline (Creb1(-/-) ) and lung epithelial-specific (Creb1(EpiΔ/Δ) ) Creb1 knockout mice showed strongly reduced Scd1, but not Fasn gene expression and protein levels in lung epithelial cells. In vitro studies using mouse MLE-15 epithelial cells showed that forskolin-mediated activation of Creb1 increased both Scd1 gene expression and protein synthesis. Additionally, MLE15 cells transfected with a dominant-negative ACreb vector blocked forskolin-mediated stimulation of Scd1 gene expression. Lipid profiling in MLE15 cells showed that dominant-negative ACreb suppressed forskolin-induced desaturation of ether linked lipids to produce plasmalogens, as well as levels of phosphatidylethanolamine, ceramide and lysophosphatidylcholine. Taken together these results demonstrate that Creb1 is essential for the induction and maintenance of Scd1 in developing fetal mouse lung epithelial cells.Nisha AntonyJacqui R WeirAnnie R A McDougallTheo MantamadiotisPeter J MeikleTimothy J ColeAnthony D BirdPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e59763 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nisha Antony Jacqui R Weir Annie R A McDougall Theo Mantamadiotis Peter J Meikle Timothy J Cole Anthony D Bird cAMP response element binding protein1 is essential for activation of steroyl co-enzyme a desaturase 1 (Scd1) in mouse lung type II epithelial cells.
description	Cyclic AMP Response Element-Binding Protein 1 (Creb1) is a transcription factor that mediates cyclic adenosine 3', 5'-monophosphate (cAMP) signalling in many tissues. Creb1(-/-) mice die at birth due to respiratory failure and previous genome-wide microarray analysis of E17.5 Creb1(-/-) fetal mouse lung identified important Creb1-regulated gene targets during lung development. The lipogenic enzymes stearoyl-CoA desaturase 1 (Scd1) and fatty acid synthase (Fasn) showed highly reduced gene expression in Creb1(-/-) lungs. We therefore hypothesized that Creb1 plays a crucial role in the transcriptional regulation of genes involved in pulmonary lipid biosynthetic pathways during lung development. In this study we confirmed that Scd1 and Fasn mRNA levels were down regulated in the E17.5 Creb1(-/-) mouse lung while the lipogenic-associated transcription factors SrebpF1, C/ebpα and Pparγ were increased. In vivo studies using germline (Creb1(-/-) ) and lung epithelial-specific (Creb1(EpiΔ/Δ) ) Creb1 knockout mice showed strongly reduced Scd1, but not Fasn gene expression and protein levels in lung epithelial cells. In vitro studies using mouse MLE-15 epithelial cells showed that forskolin-mediated activation of Creb1 increased both Scd1 gene expression and protein synthesis. Additionally, MLE15 cells transfected with a dominant-negative ACreb vector blocked forskolin-mediated stimulation of Scd1 gene expression. Lipid profiling in MLE15 cells showed that dominant-negative ACreb suppressed forskolin-induced desaturation of ether linked lipids to produce plasmalogens, as well as levels of phosphatidylethanolamine, ceramide and lysophosphatidylcholine. Taken together these results demonstrate that Creb1 is essential for the induction and maintenance of Scd1 in developing fetal mouse lung epithelial cells.
format	article
author	Nisha Antony Jacqui R Weir Annie R A McDougall Theo Mantamadiotis Peter J Meikle Timothy J Cole Anthony D Bird
author_facet	Nisha Antony Jacqui R Weir Annie R A McDougall Theo Mantamadiotis Peter J Meikle Timothy J Cole Anthony D Bird
author_sort	Nisha Antony
title	cAMP response element binding protein1 is essential for activation of steroyl co-enzyme a desaturase 1 (Scd1) in mouse lung type II epithelial cells.
title_short	cAMP response element binding protein1 is essential for activation of steroyl co-enzyme a desaturase 1 (Scd1) in mouse lung type II epithelial cells.
title_full	cAMP response element binding protein1 is essential for activation of steroyl co-enzyme a desaturase 1 (Scd1) in mouse lung type II epithelial cells.
title_fullStr	cAMP response element binding protein1 is essential for activation of steroyl co-enzyme a desaturase 1 (Scd1) in mouse lung type II epithelial cells.
title_full_unstemmed	cAMP response element binding protein1 is essential for activation of steroyl co-enzyme a desaturase 1 (Scd1) in mouse lung type II epithelial cells.
title_sort	camp response element binding protein1 is essential for activation of steroyl co-enzyme a desaturase 1 (scd1) in mouse lung type ii epithelial cells.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/95d05cfa6f7d42fd94fc268b0a632424
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cAMP response element binding protein1 is essential for activation of steroyl co-enzyme a desaturase 1 (Scd1) in mouse lung type II epithelial cells.

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