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| Status |
Public on Dec 19, 2016 |
| Title |
Loss of mouse P2Y6 nucleotide receptor is associated with physiological macrocardia and amplified pathological cardiac hypertrophy |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The study of the mechanisms leading to cardiac hypertrophy is essential to better understand cardiac development and regeneration. Pathological conditions such as ischemia or pressure overload can induce a release of extracellular nucleotides within the heart. We recently investigated the potential role of nucleotide P2Y receptors in cardiac development. We showed that adult P2Y4-null mice displayed microcardia resulting from defective cardiac angiogenesis. Here we show that loss of another P2Y subtype called P2Y6, a UDP receptor, was associated with a macrocardia phenotype and amplified pathological cardiac hypertrophy. Cardiomyocyte proliferation and size were increased in vivo in hearts of P2Y6-null neonates, resulting in enhanced post-natal heart growth. We then observed that loss of P2Y6 receptor enhanced pathological cardiac hypertrophy induced after isoproterenol injection. We identified an inhibitory effect of UDP on in vitro isoproterenol-induced cardiomyocyte hyperplasia and hypertrophy. The present study identifies mouse P2Y6 receptor as a regulator of cardiac development and cardiomyocyte function. P2Y6 receptor could constitute a therapeutic target to regulate cardiac hypertrophy.
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| Overall design |
WT and P2Y6 KO mice aged between 8 and 12 weeks were intraperitoneally injected with 50 mg/kg/day isoproterenol or saline solution, daily during 7 days, then hearts were harvested and weighted. Ventricles were then stored for RNA extraction.
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| Contributor(s) |
Clouet S, Di Pietrantonio L, Daskalopoulos E, Esfahani H, Horckmans M, Vanorlé M, Lemaire A, Balligand J, Beauloye C, Boeynaems J, Communi D |
| Citation(s) |
27231349 |
| Submission date |
Dec 21, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Frederick Libert |
| E-mail(s) |
flibert@ulb.ac.be
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| Organization name |
ULB
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| Department |
IRIBHM
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| Lab |
C2-140
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| Street address |
808 route de Lennik
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| City |
Brussels |
| ZIP/Postal code |
B-1070 |
| Country |
Belgium |
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| Platforms (1) |
| GPL18480 |
Illumina HiSeq 1500 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA306654 |
| SRA |
SRP067644 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE76215_P2Y6_KO_heart_treated-isoproterenol.csv.gz |
1.3 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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