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Phosphatidylinositol 3-Kinase–Akt Pathway Plays a Critical Role in Early Cardiomyogenesis by Regulating Canonical Wnt Signaling
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We have recently reported that activation of phosphatidylinositol 3-kinase (PI3K) plays a critical role in the early stage of cardiomyocyte differentiation of P19CL6 cells. We here examined molecular mechanisms of how PI3K is involved in cardiomyocyte differentiation. DNA chip analysis revealed that expression levels of Wnt-3a were markedly increased and that the Wnt/β-catenin pathway was activated temporally during the early stage of cardiomyocyte differentiation of P19CL6 cells. Activation of the Wnt/β-catenin pathway during this period was required and sufficient for cardiomyocyte differentiation of P19CL6 cells. Inhibition of the PI3K/Akt pathway suppressed the Wnt/β-catenin pathway by activation of glycogen synthase kinase-3β (GSK-3β) and degradation of β-catenin. Suppression of cardiomyocyte differentiation by inhibiting the PI3K/Akt pathway was rescued by forced expression of a nonphosphorylated, constitutively active form of β-catenin. These results suggest that the PI3K pathway regulates cardiomyocyte differentiation through suppressing the GSK-3β activity and maintaining the Wnt/β-catenin activity.
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“At the same time, GSK-3β also controls cell survival through regulation of β-catenin, 1 of the key molecules in Wnt signaling (11), and inhibition of Akt suppresses the Wnt pathway by activation of GSK-3β and degradation of ß-catenin (51).”
From Anabolic effect of plant brassinosteroid (2011) · cites this paper as [51]
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Cardiac Developmental Biology: From Flies to Humans
Shiojima, I., & Komuro, I. (2005) · The Japanese Journal of Physiology · doi:10.2170/jjphysiol.m94 · Cited by 7
Self-citationTu, C., Allen, A. C. B., Deng, W. W., Conroy, O., Nambiar, M., & Zoldan, J. (2018) · Experimental Cell Research · doi:10.1016/j.yexcr.2018.06.017 · Cited by 7
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Lam, J. B. B., Chow, H., Xu, A., Lam, K. S. L., Liu, J., Wong, N.-S., Moon, R. T., Shepherd, P. R., Cooper, G. J. S., & Wang, Y. (2009) · PLoS ONE · doi:10.1371/annotation/14cb7d7e-a921-4ae6-a405-99c60656579f · Cited by 6
Deng, L., Yi, S., Yin, X., Li, Y., & Luan, Q. (2022) · Stem Cells and Development · doi:10.1089/scd.2021.0316 · Cited by 5
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Metadata
- Authors
- Naito, A. T., Akazawa, H., Takano, H., Minamino, T., Nagai, T., Aburatani, H., & Komuro, I.
- Affiliations
- Chiba University (JP)
- Venue
- Circulation Research
- Published
- 2005-07-22
- Volume
- 97
- Issue
- 2
- Pages
- 144-151
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2153811819
- Cited by
- 121
- References
- 40
- Citations by year
- 2026: 2 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 7 · 2019: 3 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 6 · 2014: 5 · 2013: 9 · 2012: 9
- FWCI
- 4.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- Japan Health Sciences Foundation
- Japan Heart Foundation
- Pfizer Japan
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- phosphatidylinositol 3-kinase, Akt signaling, cardiomyocyte differentiation, cardiomyogenesis, Wnt/β-catenin signaling, Wnt3a, glycogen synthase kinase-3β, β-catenin degradation, P19CL6 cells
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Animals, Cell Differentiation, Cells, Cultured, Cytoskeletal Proteins, Dimethyl Sulfoxide, Proto-Oncogene Proteins, Signal Transduction, Trans-Activators, Protein Serine-Threonine Kinases, Phosphatidylinositol 3-Kinases, Myocytes, Cardiac, Intercellular Signaling Peptides and Proteins, Glycogen Synthase Kinase 3, Proto-Oncogene Proteins c-akt, Wnt Proteins, beta Catenin, Mice
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