title: Activation of FGF1B Promoter and FGF1 Are Involved in Cardiogenesis Through the Signaling of PKC, but Not MAPK.
abstract: Heart disease is the leading cause of human death in the 21st century. Heart transplantation is a promising way to treat this. Because donor resources are limited, cell-based therapy has been developed as an alternative. Therefore, genes that trigger cardiogenesis could have potential in the treatment of heart disease. Fibroblast growth factor 1 (FGF1) is reported to stimulate cardiomyocyte proliferation under conditions of myocardial infarction, but little is known about its function during cardiac differentiation. In this study, we established an in vitro cardiogenesis model through a reliable chemical induction protocol to determine whether FGF1 and its gene expression are involved in cardiogenesis. Oxytocin, not only a well-known hormone but also a cardiac differentiation inducer, was used in a mouse embryonic stem cell line, E14Tg2a, to achieve cardiac differentiation. After differentiation, beating cell clusters appeared and the expression of FGF1B mRNA was upregulated in the late differentiation stage (differentiation days 8-14). Interestingly, FGF1B expression patterns during cardiac differentiation were similar to those of a mature cardiomyocyte marker, troponin T2, cardiac. The blockage of FGF1-FGF receptor (FGFR) signaling reduced not only the appearance of beating cluster formation but also the expression levels of cardiomyocyte-associated genes. Moreover, by investigating FGF1 downstream signaling cascades, we observed that the efficiency of beating cluster formation was mainly regulated through the FGF1-FGFR-PKC signaling axis. Taken together, we provide evidence to support that FGF1 could regulate cardiogenesis primarily through the protein kinase C signaling, but not through the mitogen-activated protein kinase signaling, pathway.
authors.affiliation: 1 Institute of Cellular and System Medicine, National Health Research Institutes , Miaoli, Taiwan .|2 Graduate Program of Biotechnology in Medicine, Department of Life Science, Institute of Biotechnology, National Tsing Hua University , Hsinchu, Taiwan .|3 Institute of Biotechnology, National Tsing Hua University , Hsinchu, Taiwan .
authors.forename: Hung-Yu
authors.initials: HY
authors.lastname: Lin
authors.affiliation: 1 Institute of Cellular and System Medicine, National Health Research Institutes , Miaoli, Taiwan .
authors.forename: Don-Ching
authors.initials: DC
authors.lastname: Lee
authors.affiliation: 2 Graduate Program of Biotechnology in Medicine, Department of Life Science, Institute of Biotechnology, National Tsing Hua University , Hsinchu, Taiwan .|3 Institute of Biotechnology, National Tsing Hua University , Hsinchu, Taiwan .
authors.forename: Horng-Dar
authors.initials: HD
authors.lastname: Wang
authors.affiliation: 1 Institute of Cellular and System Medicine, National Health Research Institutes , Miaoli, Taiwan .|2 Graduate Program of Biotechnology in Medicine, Department of Life Science, Institute of Biotechnology, National Tsing Hua University , Hsinchu, Taiwan .
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Chi
authors.affiliation: 1 Institute of Cellular and System Medicine, National Health Research Institutes , Miaoli, Taiwan .|2 Graduate Program of Biotechnology in Medicine, Department of Life Science, Institute of Biotechnology, National Tsing Hua University , Hsinchu, Taiwan .|4 Department of Life Sciences, National Chung Hsing University , Taichung, Taiwan .
authors.forename: Ing-Ming
authors.initials: IM
authors.lastname: Chiu
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016220:Fibroblast Growth Factor 1 / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010121:Oxytocin / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism; D015290:Second Messenger Systems; D020107:Troponin T / Q000235:genetics / Q000378:metabolism
chemical_list: D017468:Receptors, Fibroblast Growth Factor; D020107:Troponin T; D016220:Fibroblast Growth Factor 1; D010121:Oxytocin; D011493:Protein Kinase C