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Prostaglandin E2 induced cardiac hypertrophy through EP2 receptor‐dependent activation of β‐catenin in 5/6 nephrectomy rats
- Source :
- ESC Heart Failure, Vol 8, Iss 3, Pp 1979-1989 (2021), ESC Heart Failure
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
Abstract
- Aims Prostaglandin E2 (PGE2) is involved in the development of cardiac hypertrophy. However, whether PGE2 regulates the chronic kidney disease‐associated cardiac hypertrophy and the tentative mechanism remains to be elucidated. Methods and results We explored the effect of PGE2 receptor inhibitors on cardiac hypertrophy in vitro and in a 5/6 nephrectomy (5/6NT) rat model using quantitative reverse transcription polymerase chain reaction, western blotting, enzyme‐linked immunosorbent assay, immunohistochemical staining, and immunofluorescence staining assays. The result showed that EP2 and EP4 receptors were both up‐regulated in the PGE2‐treated cardiomyocyte cells. PGE2 treatment enhanced active β‐catenin (non‐phosphorylated) signalling through mediating EP2 and EP4 receptors. Interestingly, inhibition of EP2 receptor suppressed PGE2‐induced cardiomyocyte hypertrophy and cardiac fibrosis‐related proteins in vitro. In the 5/6NT rat model, the increased secretion PGE2 was identified in the 5/6NT rat model for 2 weeks (P = 0.0251). EP2 receptor inhibitor administration significantly improved the cardiac function and fibrosis in 5/6NT rats. Conclusions Our study demonstrated that inhibition of EP2 receptor could improve PGE2‐induced cardiac hypertrophy in 5/6NT rats. The exploration of these mechanisms may contribute to the optimization of therapy in chronic kidney disease accompanied cardiac hypertrophy in clinic.
- Subjects :
- Cardiac function curve
5/6NT rats
medicine.medical_specialty
Prostaglandin E2 receptor
medicine.medical_treatment
Cardiomegaly
030204 cardiovascular system & hematology
Nephrectomy
Dinoprostone
03 medical and health sciences
0302 clinical medicine
Internal medicine
Original Research Articles
medicine
CKD
Animals
Diseases of the circulatory (Cardiovascular) system
030212 general & internal medicine
Original Research Article
EP2
Prostaglandin E2
Receptor
beta Catenin
Kidney
business.industry
Receptors, Prostaglandin E, EP2 Subtype
medicine.disease
Rats
Reverse transcription polymerase chain reaction
Cardiac hypertrophy
Endocrinology
medicine.anatomical_structure
Heart failure
RC666-701
lipids (amino acids, peptides, and proteins)
PGE2
Cardiology and Cardiovascular Medicine
business
Prostaglandin E
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 20555822
- Volume :
- 8
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- ESC Heart Failure
- Accession number :
- edsair.doi.dedup.....e4d86b0d769087d32716c58cfbabaac9