PUBLICATION

Cardiac injury modulates critical components of prostaglandin E2 signaling during zebrafish heart regeneration

Authors
FitzSimons, M., Beauchemin, M., Smith, A.M., Stroh, E.G., Kelpsch, D.J., Lamb, M.C., Tootle, T.L., Yin, V.P.
ID
ZDB-PUB-200225-4
Date
2020
Source
Scientific Reports   10: 3095 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Animals, Genetically Modified
  • Green Fluorescent Proteins/metabolism
  • Heart Injuries/metabolism*
  • Signal Transduction
  • Dinoprostone/metabolism*
  • Down-Regulation
  • Myocytes, Cardiac/metabolism
  • Inflammation
  • Gene Expression Regulation
  • Zebrafish
  • Cell Proliferation
  • Heart/physiology*
  • Regeneration*
  • In Situ Hybridization
  • Animals
  • Lipids/chemistry
(all 16)
PubMed
32080283 Full text @ Sci. Rep.
Abstract
The inability to effectively stimulate cardiomyocyte proliferation remains a principle barrier to regeneration in the adult human heart. A tightly regulated, acute inflammatory response mediated by a range of cell types is required to initiate regenerative processes. Prostaglandin E2 (PGE2), a potent lipid signaling molecule induced by inflammation, has been shown to promote regeneration and cell proliferation; however, the dynamics of PGE2 signaling in the context of heart regeneration remain underexplored. Here, we employ the regeneration-competent zebrafish to characterize components of the PGE2 signaling circuit following cardiac injury. In the regenerating adult heart, we documented an increase in PGE2 levels, concurrent with upregulation of cox2a and ptges, two genes critical for PGE2 synthesis. Furthermore, we identified the epicardium as the most prominent site for cox2a expression, thereby suggesting a role for this tissue as an inflammatory mediator. Injury also drove the opposing expression of PGE2 receptors, upregulating pro-restorative ptger2a and downregulating the opposing receptor ptger3. Importantly, treatment with pharmacological inhibitors of Cox2 activity suppressed both production of PGE2, and the proliferation of cardiomyocytes. These results suggest that injury-induced PGE2 signaling is key to stimulating cardiomyocyte proliferation during regeneration.
Genes / Markers
Figures
Figure Gallery (5 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
f1TgTransgenic Insertion
    pd37TgTransgenic Insertion
      w200TgTransgenic Insertion
        y1TgTransgenic Insertion
          1 - 4 of 4
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          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          No data available
          Fish
          No data available
          Antibodies
          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          DsRed2EFGDsRed2
          EGFPEFGEGFP
          GFPEFGGFP
          YFPEFGYFP
          1 - 4 of 4
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          Mapping
          No data available
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          Citation
          FitzSimons, M., Beauchemin, M., Smith, A.M., Stroh, E.G., Kelpsch, D.J., Lamb, M.C., Tootle, T.L., Yin, V.P. (2020) Cardiac injury modulates critical components of prostaglandin E2 signaling during zebrafish heart regeneration. Scientific Reports. 10:3095.