title: Cross-talk of SFRP4, integrin α1β1, and Notch1 inhibits cardiac differentiation of P19CL6 cells.
abstract: Signaling pathways play an important role in cardiogenesis. Secreted frizzled-related protein 4 (SFRP4), a member of the Wnt family, contributes to adipogenesis and tumorigenesis. However, how SFRP4 participates in cardiogenesis and the detailed molecular mechanisms involved have not been elucidated. The aim of this work was to determine cross-talk between SFRP4, integrin α1β1, and Notch1 during cardiac differentiation of P19CL6 cells. Using a well-established in vitro P19CL6 cell cardiomyocyte differentiation system, we found that SFRP4 inhibited P19CL6 cell cardiac differentiation via SFRP4 overexpression or knockdown. In addition, the SFRP4 overexpression augmented Notch1 and HES1 production. Further investigation demonstrated that SFRP4 bound to integrin α1β1 to activate the focal adhesion kinase (FAK) pathway and that phosphorylated FAK Y397 (p-FAK Y397) aided Notch intracellular domain 1 (NICD1) nuclear translocation to form a p-FAK Y397-NICD1 complex that activated the Hes1 promoter. Taken together, the cross-talk between SFRP4, integrin α1β1, and Notch1 suppresses the cardiac differentiation of P19CL6 cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education of China, Peking University, Beijing 100191, PR China.
authors.forename: Yuyao
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education of China, Peking University, Beijing 100191, PR China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education of China, Peking University, Beijing 100191, PR China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education of China, Peking University, Beijing 100191, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education of China, Peking University, Beijing 100191, PR China.
authors.forename: Kangtao
authors.initials: K
authors.lastname: Ma
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education of China, Peking University, Beijing 100191, PR China. Electronic address: zhuqingjia@bjmu.edu.cn.
authors.forename: Zhuqing
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education of China, Peking University, Beijing 100191, PR China. Electronic address: chunyanzhou@bjmu.edu.cn.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D039222:Integrin alpha1beta1 / Q000378:metabolism*; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D000072056:Transcription Factor HES-1; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D051416:Focal Adhesion Protein-Tyrosine Kinases; D039222:Integrin alpha1beta1; D011518:Proto-Oncogene Proteins; D051880:Receptors, Notch; D000072056:Transcription Factor HES-1; C489734:Hes1 protein, mouse; C498454:Sfrp4 protein, mouse; D000094742:Secreted Frizzled-Related Proteins
keywords: Cardiac differentiation; Integrin α1β1; Notch1; SFRP4