Reciprocal regulation of miR-23a and lysophosphatidic acid receptor signaling in cardiomyocyte hypertrophy
Abstract
Earlier, our study demonstrated that lysophosphatidic acid (LPA) receptor mediated cardiomyocyte hypertrophy. However, the subtype-specific functions for LPA1 and LPA3 receptors in LPA-induced hypertrophy have not been distinguished. Growing evidence indicates that microRNAs (miRNAs) are involved in the pathogenesis of cardiac hypertrophy by down-regulating target molecules. The present work therefore aimed at elucidating the functions mediated by different subtypes of LPA receptors and investigating the modulatory role of miRNAs during LPA induced hypertrophy. Experiments were done with cultured neonatal rat cardiomyocytes (NRCMs) exposed to LPA and we showed that knockdown of LPA1 by small interfering RNA (siRNA) enhanced LPA-induced cardiomyocyte hypertrophy, whereas LPA3 silencing repressed hypertrophy. miR-23a, a pro-hypertrophic miRNA, was up-regulated by LPA in cardiomyocytes and its down-regulation reduced LPA-induced cardiomyocyte hypertrophy. Importantly, luciferase reporter assay confirmed LPA1 to be a target of miR-23a, indicating that miR-23a is involved in mediating the LPA-induced cardiomyocyte hypertrophy by targeting LPA1. In addition, knockdown of LPA3, but not LPA1, eliminated miR-23a elevation induced by LPA. And PI3K inhibitor, LY294002, effectively prevented LPA-induced miR-23a expression in cardiomyocytes, suggesting that LPA might induce miR-23a elevation by activating LPA3 and PI3K/AKT pathway. These findings identified opposite subtype-specific funct…
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miR-23a increases in mediating lysophosphatidic acid-induced cardiomyocyte hypertrophy, with LPA1 as the direct target, and miR-23a elevation can be restrained by PI3K inhibitors.
“It was confirmed that miR-23a increased in mediating the lysophosphatidic acid (LPA) -induced cardiomyocyte hypertrophy, LPA1 was the direct target, however, miR-23a elevation can be restrained by PI3K inhibitors [52].”
From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [52]
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microRNAs as critical regulators in heart development and diseases
Rani, V. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-91305-8.00005-3
- Authors
- Yang, J., Nie, Y., Wang, F., Hou, J., Cong, X., Hu, S., & Chen, X.
- Affiliations
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Corresponding author
- Chen, Xi
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
- Publisher
- Elsevier BV
- Published
- 2013-08
- Volume
- 1831
- Issue
- 8
- Pages
- 1386-1394
- ISSN
- 1388-1981 (ISSN-L)
- OpenAlex
- W1971681998
- Cited by
- 30
- References
- 41
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 1 · 2022: 2 · 2020: 2 · 2019: 4 · 2018: 4 · 2017: 6 · 2016: 2 · 2015: 2 · 2014: 3
- FWCI
- 1.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- miR-23a, lysophosphatidic acid, LPA1 receptor, LPA3 receptor, cardiomyocyte hypertrophy, microRNA regulation, PI3K/Akt signaling, receptor subtype specificity, neonatal rat cardiomyocytes, lipid signaling
- MeSH terms
- Phosphoinositide-3 Kinase Inhibitors, Animals, Cells, Cultured, Chromones, Enzyme Inhibitors, Gene Expression Regulation, Cardiomegaly, Humans, Lysophospholipids, Morpholines, Muscle Proteins, Signal Transduction, Rats, Sprague-Dawley, Phosphatidylinositol 3-Kinases, Myocytes, Cardiac, MicroRNAs, Receptors, Lysophosphatidic Acid, Proto-Oncogene Proteins c-akt, Rats
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