Increased cardiogenesis in P19-GFP teratocarcinoma cells expressing the propeptide IGF-1Ea

• Published in: Biochemical and biophysical research communications 2011-12, Vol.416 (3-4), p.293-299
• Main Authors: Poudel, Bhawana, Bilbao, Daniel, Sarathchandra, Padmini, Germack, Renee, Rosenthal, Nadia, Santini, Maria Paola
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; Animals; CARCINOMAS; Cardiac differentiation; Cell Cycle; Cell Differentiation; Cell Line, Tumor; CELL PROLIFERATION; Cell Survival; DMSO; GENE THERAPY; GROWTH FACTORS; HEART; Heart - embryology; IGF-1Ea; IN VITRO; IN VIVO; INSULIN; Insulin-Like Growth Factor I - biosynthesis; Insulin-Like Growth Factor I - genetics; Mesoderm - embryology; Mice; Myocytes, Cardiac - cytology; Organogenesis; Peptides - genetics; Pluripotent stem cells; Pluripotent Stem Cells - metabolism; Protein Serine-Threonine Kinases; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; STEM CELLS
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2011.11.028

► In this study, we explored the function of IGF-1Ea propeptide in inducing cardiogenesis of stem cells. ► IGF-1Ea promoted cardiac mesodermal induction in uncommitted cells. ► Under differentiation condition, IGF-1Ea increased expression of cardiac differentiation markers. ► Furthermore, it promoted formation of finely organized sarcomeric structure. ► IGF-1Ea propeptide may be a good candidate to improve production of cardiomyocytes from pluripotent cells. The mechanism implicated in differentiation of endogenous cardiac stem cells into cardiomyocytes to regenerate the heart tissue upon an insult remains elusive, limiting the therapeutical goals to exogenous cell injection and/or gene therapy. We have shown previously that cardiac specific overexpression of the insulin-like growth factor 1 propeptide IGF-1Ea induces beneficial myocardial repair after infarct. Although the mechanism is still under investigation, the possibility that this propeptide may be involved in promoting stem cell differentiation into the cardiac lineage has yet to be explored. To investigate whether IGF-1Ea promote cardiogenesis, we initially modified P19 embryonal carcinoma cells to express IGF-1Ea. Taking advantage of their cardiomyogenic nature, we analyzed whether overexpression of this propeptide affected cardiac differentiation program. The data herein presented showed for the first time that constitutively overexpressed IGF-1Ea increased cardiogenic differentiation program in both undifferentiated and DMSO-differentiated cells. In details, IGF-1Ea overexpression promoted localization of alpha-actinin in finely organized sarcomeric structure compared to control cells and upregulated the cardiac mesodermal marker NKX-2.5 and the ventricular structural protein MLC2v. Furthermore, activated IGF-1 signaling promoted cardiac mesodermal induction in undifferentiated cells independently of cell proliferation. This analysis suggests that IGF-1Ea may be a good candidate to improve both in vitro production of cardiomyocytes from pluripotent stem cells and in vivo activation of the differentiation program of cardiac progenitor cells.