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COL6A3 expression in adipose tissue cells is associated with levels of the homeobox transcription factor PRRX1

Fibrillar collagen COL6α3 in adipose tissue has been associated with obesity, inflammation, insulin resistance and cancer. We here aimed to identify novel transcriptional regulators of COL6A3 expression. Based on a transcriptome dataset of adipose tissue, we identified strong correlations for 56 gen...

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Autores principales: Dankel, Simon N., Grytten, Elise, Bjune, Jan-Inge, Nielsen, Hans Jørgen, Dietrich, Arne, Blüher, Matthias, Sagen, Jørn V., Mellgren, Gunnar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678848/
https://www.ncbi.nlm.nih.gov/pubmed/33214660
http://dx.doi.org/10.1038/s41598-020-77406-2
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author Dankel, Simon N.
Grytten, Elise
Bjune, Jan-Inge
Nielsen, Hans Jørgen
Dietrich, Arne
Blüher, Matthias
Sagen, Jørn V.
Mellgren, Gunnar
author_facet Dankel, Simon N.
Grytten, Elise
Bjune, Jan-Inge
Nielsen, Hans Jørgen
Dietrich, Arne
Blüher, Matthias
Sagen, Jørn V.
Mellgren, Gunnar
author_sort Dankel, Simon N.
collection PubMed
description Fibrillar collagen COL6α3 in adipose tissue has been associated with obesity, inflammation, insulin resistance and cancer. We here aimed to identify novel transcriptional regulators of COL6A3 expression. Based on a transcriptome dataset of adipose tissue, we identified strong correlations for 56 genes with COL6A3 mRNA, including targets of TGF-β/SMAD signaling. Among the identified candidates, the homeobox transcription factor PRRX1 showed a particularly striking co-expression with COL6A3, validated across several different cohorts, including patients with extreme obesity, insulin sensitive and resistant obesity (subcutaneous and omental), after profound fat loss (subcutaneous), and lean controls (subcutaneous). In human and mouse adipose cells, PRRX1 knockdown reduced COL6A3 mRNA and PRRX1 overexpression transactivated a reporter construct with the endogenous human COL6A3 promoter. Stable PRRX1 overexpression in 3T3-L1 cells induced Col6a3 mRNA threefold specifically after adipogenic induction, whereas TGF-β1 treatment upregulated Col6a3 mRNA also in the preadipocyte state. Interestingly, pro-inflammatory stimulus (i.e., TNF-α treatment) decreased PRRX1-mediated Col6a3 transactivation and mRNA expression, supporting a role for this mechanism in the regulation of adipose tissue inflammation. In conclusion, we identified the homeobox factor PRRX1 as a novel transcriptional regulator associated with COL6A3 expression, providing new insight into the regulatory mechanisms of altered adipose tissue function in obesity and insulin resistance.
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spelling pubmed-76788482020-11-23 COL6A3 expression in adipose tissue cells is associated with levels of the homeobox transcription factor PRRX1 Dankel, Simon N. Grytten, Elise Bjune, Jan-Inge Nielsen, Hans Jørgen Dietrich, Arne Blüher, Matthias Sagen, Jørn V. Mellgren, Gunnar Sci Rep Article Fibrillar collagen COL6α3 in adipose tissue has been associated with obesity, inflammation, insulin resistance and cancer. We here aimed to identify novel transcriptional regulators of COL6A3 expression. Based on a transcriptome dataset of adipose tissue, we identified strong correlations for 56 genes with COL6A3 mRNA, including targets of TGF-β/SMAD signaling. Among the identified candidates, the homeobox transcription factor PRRX1 showed a particularly striking co-expression with COL6A3, validated across several different cohorts, including patients with extreme obesity, insulin sensitive and resistant obesity (subcutaneous and omental), after profound fat loss (subcutaneous), and lean controls (subcutaneous). In human and mouse adipose cells, PRRX1 knockdown reduced COL6A3 mRNA and PRRX1 overexpression transactivated a reporter construct with the endogenous human COL6A3 promoter. Stable PRRX1 overexpression in 3T3-L1 cells induced Col6a3 mRNA threefold specifically after adipogenic induction, whereas TGF-β1 treatment upregulated Col6a3 mRNA also in the preadipocyte state. Interestingly, pro-inflammatory stimulus (i.e., TNF-α treatment) decreased PRRX1-mediated Col6a3 transactivation and mRNA expression, supporting a role for this mechanism in the regulation of adipose tissue inflammation. In conclusion, we identified the homeobox factor PRRX1 as a novel transcriptional regulator associated with COL6A3 expression, providing new insight into the regulatory mechanisms of altered adipose tissue function in obesity and insulin resistance. Nature Publishing Group UK 2020-11-19 /pmc/articles/PMC7678848/ /pubmed/33214660 http://dx.doi.org/10.1038/s41598-020-77406-2 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Dankel, Simon N.
Grytten, Elise
Bjune, Jan-Inge
Nielsen, Hans Jørgen
Dietrich, Arne
Blüher, Matthias
Sagen, Jørn V.
Mellgren, Gunnar
COL6A3 expression in adipose tissue cells is associated with levels of the homeobox transcription factor PRRX1
title COL6A3 expression in adipose tissue cells is associated with levels of the homeobox transcription factor PRRX1
title_full COL6A3 expression in adipose tissue cells is associated with levels of the homeobox transcription factor PRRX1
title_fullStr COL6A3 expression in adipose tissue cells is associated with levels of the homeobox transcription factor PRRX1
title_full_unstemmed COL6A3 expression in adipose tissue cells is associated with levels of the homeobox transcription factor PRRX1
title_short COL6A3 expression in adipose tissue cells is associated with levels of the homeobox transcription factor PRRX1
title_sort col6a3 expression in adipose tissue cells is associated with levels of the homeobox transcription factor prrx1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678848/
https://www.ncbi.nlm.nih.gov/pubmed/33214660
http://dx.doi.org/10.1038/s41598-020-77406-2
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