Macrophage Kdm6b controls the pro-fibrotic transcriptome signature of foam cells

Annette E. Neele, Koen H. M. Prange, Marten A. Hoeksema, Saskia van der Velden, Tina Lucas, Stefanie Dimmeler, Esther Lutgens, Jan van den Bossche, Menno P. J. de Winther

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Aim: In order to identify regulators of foam cells, we studied the H3K27 demethylase Kdm6b (also known as Jmjd3), a known regulator of macrophages, in controlling the transcriptional profile of foam cells. Materials & methods: Foam cells from Kdm6b-deleted or Kdm6b wild-type mice were isolated and used for RNA-sequencing analysis. Results: Pathway analysis revealed that pro-fibrotic pathways were strongly suppressed in Kdm6b-deleted foam cells. Analysis of published datasets showed that foam cell formation induces these pro-fibrotic characteristics. Overlay of both datasets indicated that fibrotic genes which are induced upon foam cell formation, are reduced in the absence of Kdm6b. These data suggest that foam cell formation induces a pro-fibrotic gene signature in a Kdm6b-dependent manner. Conclusion: We identified Kdm6b as a novel regulator of the pro-fibrotic signature of peritoneal foam cells.
Original languageEnglish
Pages (from-to)383-391
Number of pages9
JournalEpigenomics
Volume9
Issue number4
DOIs
Publication statusPublished - 2017
Externally publishedYes

Cite this

Neele, A. E., Prange, K. H. M., Hoeksema, M. A., van der Velden, S., Lucas, T., Dimmeler, S., ... de Winther, M. P. J. (2017). Macrophage Kdm6b controls the pro-fibrotic transcriptome signature of foam cells. Epigenomics, 9(4), 383-391. https://doi.org/10.2217/epi-2016-0152
Neele, Annette E. ; Prange, Koen H. M. ; Hoeksema, Marten A. ; van der Velden, Saskia ; Lucas, Tina ; Dimmeler, Stefanie ; Lutgens, Esther ; van den Bossche, Jan ; de Winther, Menno P. J. / Macrophage Kdm6b controls the pro-fibrotic transcriptome signature of foam cells. In: Epigenomics. 2017 ; Vol. 9, No. 4. pp. 383-391.
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abstract = "Aim: In order to identify regulators of foam cells, we studied the H3K27 demethylase Kdm6b (also known as Jmjd3), a known regulator of macrophages, in controlling the transcriptional profile of foam cells. Materials & methods: Foam cells from Kdm6b-deleted or Kdm6b wild-type mice were isolated and used for RNA-sequencing analysis. Results: Pathway analysis revealed that pro-fibrotic pathways were strongly suppressed in Kdm6b-deleted foam cells. Analysis of published datasets showed that foam cell formation induces these pro-fibrotic characteristics. Overlay of both datasets indicated that fibrotic genes which are induced upon foam cell formation, are reduced in the absence of Kdm6b. These data suggest that foam cell formation induces a pro-fibrotic gene signature in a Kdm6b-dependent manner. Conclusion: We identified Kdm6b as a novel regulator of the pro-fibrotic signature of peritoneal foam cells.",
keywords = "Jmjd3, JmjdC, Kdm6b, epigenetics, fibrosis, histone H3K27me3, histone demethylase, histone modification, macrophage, matrix biology",
author = "Neele, {Annette E.} and Prange, {Koen H. M.} and Hoeksema, {Marten A.} and {van der Velden}, Saskia and Tina Lucas and Stefanie Dimmeler and Esther Lutgens and {van den Bossche}, Jan and {de Winther}, {Menno P. J.}",
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Neele, AE, Prange, KHM, Hoeksema, MA, van der Velden, S, Lucas, T, Dimmeler, S, Lutgens, E, van den Bossche, J & de Winther, MPJ 2017, 'Macrophage Kdm6b controls the pro-fibrotic transcriptome signature of foam cells' Epigenomics, vol. 9, no. 4, pp. 383-391. https://doi.org/10.2217/epi-2016-0152

Macrophage Kdm6b controls the pro-fibrotic transcriptome signature of foam cells. / Neele, Annette E.; Prange, Koen H. M.; Hoeksema, Marten A.; van der Velden, Saskia; Lucas, Tina; Dimmeler, Stefanie; Lutgens, Esther; van den Bossche, Jan; de Winther, Menno P. J.

In: Epigenomics, Vol. 9, No. 4, 2017, p. 383-391.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Neele, Annette E.

AU - Prange, Koen H. M.

AU - Hoeksema, Marten A.

AU - van der Velden, Saskia

AU - Lucas, Tina

AU - Dimmeler, Stefanie

AU - Lutgens, Esther

AU - van den Bossche, Jan

AU - de Winther, Menno P. J.

PY - 2017

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AB - Aim: In order to identify regulators of foam cells, we studied the H3K27 demethylase Kdm6b (also known as Jmjd3), a known regulator of macrophages, in controlling the transcriptional profile of foam cells. Materials & methods: Foam cells from Kdm6b-deleted or Kdm6b wild-type mice were isolated and used for RNA-sequencing analysis. Results: Pathway analysis revealed that pro-fibrotic pathways were strongly suppressed in Kdm6b-deleted foam cells. Analysis of published datasets showed that foam cell formation induces these pro-fibrotic characteristics. Overlay of both datasets indicated that fibrotic genes which are induced upon foam cell formation, are reduced in the absence of Kdm6b. These data suggest that foam cell formation induces a pro-fibrotic gene signature in a Kdm6b-dependent manner. Conclusion: We identified Kdm6b as a novel regulator of the pro-fibrotic signature of peritoneal foam cells.

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KW - matrix biology

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SN - 1750-1911

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Neele AE, Prange KHM, Hoeksema MA, van der Velden S, Lucas T, Dimmeler S et al. Macrophage Kdm6b controls the pro-fibrotic transcriptome signature of foam cells. Epigenomics. 2017;9(4):383-391. https://doi.org/10.2217/epi-2016-0152