B. Koskulu1,2, R. J. Schwartz3 1Baylor College Of Medicine, Houston, TX, USA 2University Of Houston, Pharmacy, Houston, TX, USA 3University Of Houston, Biochemistry, Houston, TX, USA
Introduction: A heart injury can cause damage to cardiac muscle tissue, which cannot be repaired due to the low rate of proliferation in cardiac myocytes. A promising approach to healing the cardiac muscle tissue involves inducing cardiomyocyte growth by reactivating the cell proliferation signaling mechanisms. Sphingosine-1-phosphate (S1P), a bioactive lipid molecule, shows promise in inducing cell proliferation. S1P triggers cell signaling through G-protein coupled receptors (S1PRs) and initiates several signaling pathways, including growth, differentiation, migration, and proliferation.
Methods: We utilized the S1P molecule to induce cardiomyocyte-like cells with very low proliferation capacity upon differentiation, mimicking the low proliferating myocardial cells. The effect of S1P on cell proliferation was assessed using a wound healing assay and imaged with a fluorescent microscope to observe nuclear division. Time-course analysis of cell division transcriptomes was conducted using qPCR assays. Subsequently, RNA sequencing of different time points after S1P addition was performed to identify the cellular response to proliferation.
Results: Our research demonstrated that S1P signaling induces cell cycle entry from G1 to S. Fluorescent images revealed that cell division was initiated and nuclei division was completed within 24 hours after S1P addition. Several cell cycle transcript levels changed in response to S1P addition. Data from RNA sequencing indicated that pathways such as Notch, Wnt, Erk, and Hippo, as well as physiological events like cell cycle initiation and wound healing, were regulated. Furthermore, S1P signaling played a key role in telomere preservation and elongation.
Conclusion: Therefore, S1P is an important signaling molecule for inducing cardiomyocyte growth, proliferation, and other critical cellular processes such as wound healing and telomere maintenance.