title: Silencing of nodal modulator 1 inhibits the differentiation of P19 cells into cardiomyocytes.
abstract: Nodal modulator 1 (NOMO1), a highly conserved transmembrane protein, has been identified as a part of a protein complex that participates in the Nodal signaling pathway, a critical determinant of heart and visceral organ formation. We previously found that the NOMO1 gene was substantially downregulated in human ventricular septal defect (VSD) myocardium and, thus, may be an important molecular pathway in human heart development. In this study, we aimed to investigate the effects of NOMO1 gene silencing by RNA interference (RNAi) during early mouse cardiac differentiation using P19 cells as a model system. Our results revealed that the differentiated P19 cell population exhibited downregulated NOMO1 levels and expressed lower levels of Nodal signaling mediators, such as Nodal, Cripto and Smad2, than the negative control. Similarly, cardiomyocyte-specific sarcomeric markers, such as cardiac troponin T, as well as expression of cardiogenesis-related transcriptional factors, such as Nkx2.5, Gata4 and Tbx5 were found to be downregulated in P19 differentiated cardiomyocytes in NOMO1-silenced cells when compared to controls. In conclusion, our results indicate that NOMO1 gene knockdown inhibits the differentiation of P19 cells into cardiomyocytes, which highlights a potential role for NOMO1 in early cardiogenesis.
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing 210029, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Yancheng City No. 1 People׳s Hospital, Yancheng, Jiangsu 224001, China.
authors.forename: Chunyang
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing 210029, China. Electronic address: yr@njmu.edu.cn.
authors.forename: Rong
authors.initials: R
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing 210029, China. Electronic address: huanhuanchen@hotmail.com.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing 210029, China.
authors.forename: Xiangqing
authors.initials: X
authors.lastname: Kong
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing 210029, China.
authors.forename: Linmei
authors.initials: L
authors.lastname: Qian
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing 210029, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Sheng
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing 210029, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D015536:Down-Regulation; D004815:Epidermal Growth Factor / Q000096:biosynthesis / Q000235:genetics; D050991:GATA4 Transcription Factor / Q000096:biosynthesis / Q000235:genetics; D006321:Heart / Q000196:embryology*; D006345:Heart Septal Defects, Ventricular / Q000235:genetics; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D055457:Nodal Protein / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000235:genetics; D051899:Smad2 Protein / Q000096:biosynthesis / Q000235:genetics; D020825:T-Box Domain Proteins / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D020107:Troponin T / Q000096:biosynthesis / Q000235:genetics
chemical_list: D050991:GATA4 Transcription Factor; C484171:Gata4 protein, mouse; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C484469:Nkx2-5 protein, mouse; D055457:Nodal Protein; C526008:Nodal protein, mouse; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5; C489450:Tdgf1 protein, mouse; D014157:Transcription Factors; D020107:Troponin T; D004815:Epidermal Growth Factor
keywords: Congenital heart disease; NOMO1; P19 cells; RNA interference