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Macrophage Kdm6b controls the pro-fibrotic transcriptome signature of foam cells
Annette E Neele1, Koen Hm Prange1, Marten A Hoeksema1
1Department of Medical Biochemistry, Experimental Vascular Biology, Academic Medical Center, Amsterdam, The Netherlands.
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.
Insights
The histone demethylase Kdm6b regulates the pro-fibrotic gene signature in foam cells. Deleting Kdm6b suppresses these fibrotic pathways, suggesting Kdm6b is a key regulator of foam cell-induced fibrosis.
Area of Science:
- Cell Biology
- Molecular Biology
- Epigenetics
Background:
- Foam cells are key players in atherosclerosis and fibrosis.
- Macrophage regulators are crucial for understanding foam cell function.
- Kdm6b (Jmjd3) is an H3K27 demethylase known to regulate macrophages.
Purpose of the Study:
- To investigate the role of Kdm6b in regulating the transcriptional profile of foam cells.
- To identify regulators of foam cell-induced pro-fibrotic characteristics.
Main Methods:
- Isolation of foam cells from Kdm6b-deleted and wild-type mice.
- RNA-sequencing analysis of isolated foam cells.
- Pathway analysis and comparison with published datasets.
Main Results:
- Kdm6b deletion significantly suppressed pro-fibrotic pathways in foam cells.
- Foam cell formation was found to induce pro-fibrotic characteristics.
- Fibrotic genes induced by foam cell formation were reduced in Kdm6b-deficient foam cells.
Conclusions:
- Kdm6b is identified as a novel regulator of the pro-fibrotic signature in peritoneal foam cells.
- Foam cell formation induces a pro-fibrotic gene signature in a Kdm6b-dependent manner.
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