Silencing of sphingosine kinase 1 affects maturation pathways in mouse neonatal cardiomyocytes

Jozefczuk, E., Szczepaniak, P., Guzik, T. J. and Siedlinski, M. (2021) Silencing of sphingosine kinase 1 affects maturation pathways in mouse neonatal cardiomyocytes. International Journal of Molecular Sciences, 22(7), 3616. (doi: 10.3390/ijms22073616) (PMID:33807180) (PMCID:PMC8037404)

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Sphingosine kinase-1 (Sphk1) and its product, sphingosine-1-phosphate (S1P) are important regulators of cardiac growth and function. Numerous studies have reported that Sphk1/S1P signaling is essential for embryonic cardiac development and promotes pathological cardiac hypertrophy in adulthood. However, no studies have addressed the role of Sphk1 in postnatal cardiomyocyte (CM) development so far. The present study aimed to assess the molecular mechanism(s) by which Sphk1 silencing might influence CMs development and hypertrophy in vitro. Neonatal mouse CMs were transfected with siRNA against Sphk1 or negative control, and subsequently treated with 1 µM angiotensin II (AngII) or a control buffer for 24 h. The results of RNASeq analysis revealed that diminished expression of Sphk1 significantly accelerated neonatal CM maturation by inhibiting cell proliferation and inducing developmental pathways in the stress (AngII-induced) conditions. Importantly, similar effects were observed in the control conditions. Enhanced maturation of Sphk1-lacking CMs was further confirmed by the upregulation of the physiological hypertrophy-related signaling pathway involving Akt and downstream glycogen synthase kinase 3 beta (Gsk3β) downregulation. In summary, we demonstrated that the Sphk1 silencing in neonatal mouse CMs facilitated their postnatal maturation in both physiological and stress conditions.

Item Type:Articles
Additional Information:This work was funded by the National Science Centre (Poland), grant No. 2016/22/E/NZ4/ 00610 to M.S., Ministry of Science and Higher Education (Poland) grants Nos N41/DBS/000243 and N41/DBS/000115 to M.S. and E.J., respectively, and Priority Research Area qLife under the program “Excellence Initiative—Research University” at the Jagiellonian University in Krakow.
Keywords:Sphingosine kinase-1, sphingosine-1-phosphate, cardiomyocyte, cardiomyocyte hypertrophy, cardiomyocyte maturation, cardiomyocyte proliferation.
Glasgow Author(s) Enlighten ID:Szczepaniak, Mr Piotr and Siedlinski, Mr Mateusz and Guzik, Professor Tomasz
Creator Roles:
Szczepaniak, P.Investigation, Methodology
Guzik, T. J.Supervision
Siedlinski, M.Conceptualization, Formal analysis, Funding acquisition, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – review and editing
Authors: Jozefczuk, E., Szczepaniak, P., Guzik, T. J., and Siedlinski, M.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:International Journal of Molecular Sciences
ISSN (Online):1422-0067
Published Online:31 March 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in International Journal of Molecular Sciences 22(7): 3616
Publisher Policy:Reproduced under a Creative Commons License

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