title: Eosinophil cationic protein enhances cardiomyocyte differentiation of P19CL6 embryonal carcinoma cells by stimulating the FGF receptor signaling pathway.
abstract: We investigated the functional role of eosinophil cationic protein (ECP) in regulating cardiomyogenesis using mouse P19CL6 embryonic carcinoma cells. ECP was confirmed to accelerate the cardiomyocyte differentiation of P19CL6 cells by enhancing the rate and area size of beating of cardiomyocyte and by facilitating the expression of cardiomyocyte-specific genes, such as GATA4 and α-MHC. Since cardiomyocyte differentiation in vivo is considered to follow mesoderm induction, the induction of Brachyury, a marker of mesoderm, was assessed. Brachyury expression was found to be enhanced after the addition of ECP. This enhancement was due to the stimulation of extracellular signal-regulated kinase (ERK)1/2 phosphorylation by ECP. In this context, treatment with SU5402, an inhibitor of fibroblast growth factor (FGF) receptor 1, suppressed Brachyury expression, phosphorylation of ERK1/2, and cardiomyocyte differentiation induced by ECP. We concluded that ECP might induce mesoderm differentiation through FGF signaling pathway and enhance subsequent cardiomyocyte differentiation in concert with dimethyl sulfoxide in P19CL6 cells. ECP may be a novel factor for cardiomyocyte differentiation, which should be very useful to prepare adequate numbers of cardiomyocytes for therapeutic cell transplantation.
authors: Laboratory of Nano-Biotechnology, Department of Medical Bioengineering Science, Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530, Japan.
authors: Guoliang
authors: G
authors: Jin
authors: Akifumi
authors: A
authors: Mizutani
authors: Takayuki
authors: T
authors: Fukuda
authors: Ling
authors: L
authors: Chen
authors: Keisuke
authors: K
authors: Nakanishi
authors: Ting
authors: T
authors: Yan
authors: Takayuki
authors: T
authors: Kudoh
authors: Satoshi
authors: S
authors: Hirohata
authors: Tomonari
authors: T
authors: Kasai
authors: Hiroshi
authors: H
authors: Murakami
authors: David S
authors: DS
authors: Salomon
authors: Masaharu
authors: M
authors: Seno
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D054278:Embryonal Carcinoma Stem Cells / Q000166:cytology* / Q000378:metabolism; D047150:Eosinophil Cationic Protein / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005326:Fetal Proteins / Q000096:biosynthesis; D050991:GATA4 Transcription Factor / Q000096:biosynthesis; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000096:biosynthesis; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000494:pharmacology; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000096:biosynthesis; D000098908:Brachyury Protein
chemical_list: D004121:Dimethyl Sulfoxide; D047150:Eosinophil Cationic Protein; D048049:Extracellular Signal-Regulated MAP Kinases; D005326:Fetal Proteins; D050991:GATA4 Transcription Factor; D018995:Myosin Heavy Chains; D011505:Protein-Tyrosine Kinases; D011758:Pyrroles; D017468:Receptors, Fibroblast Growth Factor; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein; C484171:Gata4 protein, mouse; C105686:SU 5402