Journal article
Cardiac injury modulates critical components of prostaglandin E2 signaling during zebrafish heart regeneration
Scientific reports, Vol.10(1), pp.3095-3095
02/20/2020
DOI: 10.1038/s41598-020-59868-6
PMCID: PMC7033201
PMID: 32080283
Abstract
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 E
2
(PGE
2
), a potent lipid signaling molecule induced by inflammation, has been shown to promote regeneration and cell proliferation; however, the dynamics of PGE
2
signaling in the context of heart regeneration remain underexplored. Here, we employ the regeneration-competent zebrafish to characterize components of the PGE
2
signaling circuit following cardiac injury. In the regenerating adult heart, we documented an increase in PGE
2
levels, concurrent with upregulation of
cox2a
and
ptges
, two genes critical for PGE
2
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 PGE
2
receptors, upregulating pro-restorative
ptger2a
and downregulating the opposing receptor
ptger3
. Importantly, treatment with pharmacological inhibitors of Cox2 activity suppressed both production of PGE
2
, and the proliferation of cardiomyocytes. These results suggest that injury-induced PGE
2
signaling is key to stimulating cardiomyocyte proliferation during regeneration.
Details
- Title: Subtitle
- Cardiac injury modulates critical components of prostaglandin E2 signaling during zebrafish heart regeneration
- Creators
- MaryLynn FitzSimons - University of MaineMegan Beauchemin - University of MaineAshley M. Smith - Mount Desert Island Biological LaboratoryErika G. Stroh - Mount Desert Island Biological LaboratoryDaniel J. Kelpsch - Carnegie Institution for ScienceMaureen C. Lamb - Roy J. and Lucille A. Carver College of MedicineTina L. Tootle - Roy J. and Lucille A. Carver College of MedicineViravuth P. Yin - University of Maine
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.10(1), pp.3095-3095
- DOI
- 10.1038/s41598-020-59868-6
- PMID
- 32080283
- PMCID
- PMC7033201
- NLM abbreviation
- Sci Rep
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Grant note
- DOI: 10.13039/100000002, name: U.S. Department of Health & Human Services | National Institutes of Health, award: P20 GM104318, P20 GM10342; name: U.S. Department of Health & Human Services | National Institutes of Health; DOI: 10.13039/100000968, name: American Heart Association, award: 11SDG7210045; name: MacKenzie Foundation 17003
- Language
- English
- Date published
- 02/20/2020
- Academic Unit
- Anatomy and Cell Biology
- Record Identifier
- 9984284458302771
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