title: Long noncoding RNA Braveheart promotes cardiogenic differentiation of mesenchymal stem cells in vitro.
abstract: Mesenchymal stem cells (MSCs) have limited potential of cardiogenic differentiation. In this study, we investigated the influence of long noncoding RNA Braveheart (lncRNA-Bvht) on cardiogenic differentiation of MSCs in vitro.
  
  
  
  MSCs were obtained from C57BL/6 mice and cultured in vitro. Cells were divided into three groups: blank control, null vector control, and lncRNA-Bvht. All three groups experienced exposure to hypoxia (1% O2) and serum deprivation for 24 h, and 24 h of reoxygenation (20% O2). Cardiogenic differentiation was induced using 5-AZA for another 24 h. Normoxia (20% O2) was applied as a negative control during the whole process. Cardiogenic differentiation was assessed, and expressions of cardiac-specific transcription factors and epithelial-mesenchymal transition (EMT)-associated biomarkers were detected. Anti-mesoderm posterior1 (Mesp1) siRNA was transfected in order to block its expression, and relevant downstream molecules were examined.
  
  
  
  Compared with the blank control and null vector control groups, the lncRNA-Bvht group presented a higher percentage of differentiated cells of the cardiogenic phenotype in vitro both under the normal condition and after hypoxia/re-oxygenation. There was an increased level of cTnT and α-SA, and cardiac-specific transcription factors including Nkx2.5, Gata4, Gata6, and Isl-1 were significantly upregulated (P < 0.01). Expressions of EMT-associated genes including Snail, Twist and N-cadherin were much higher (P < 0.01). Mesp1 exhibited a distinct augmentation following lncRNA-Bvht transfection. Expressions of relevant cardiac-specific transcription factors and EMT-associated genes all presented a converse alteration in the condition of Mesp1 inhibition prior to lncRNA-Bvht transfection.
  
  
  
  lncRNA-Bvht could efficiently promote MSCs transdifferentation into cells with the cardiogenic phenotype in vitro. It might function via enhancing the expressions of cardiac-specific transcription factors and EMT-associated genes. Mesp1 could be a pivotal intermediary in the procedure.
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.|Department of Emergency, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.
authors.forename: Jingying
authors.initials: J
authors.lastname: Hou
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.|Department of Emergency, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.
authors.forename: Huibao
authors.initials: H
authors.lastname: Long
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.|Department of Emergency, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.|Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, 107 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.
authors.forename: Shaoxin
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.|Department of Emergency, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.|Department of Emergency, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.
authors.forename: Tianzhu
authors.initials: T
authors.lastname: Guo
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.|Department of Emergency, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.
authors.forename: Quanhua
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.|Department of Emergency, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhong
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China. tongwang316@163.com.|Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, 107 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China. tongwang316@163.com.|Department of Emergency, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong, 510120, China. tongwang316@163.com.
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002319:Cardiovascular System / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D002454:Cell Differentiation; D058732:Embryoid Bodies / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D008648:Mesoderm / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D038081:Organogenesis / Q000235:genetics; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D063151:Polycomb Repressive Complex 2; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; C101538:Mesp1 protein, mouse; C494163:Suz12 protein, mouse
keywords: Cardiac specific transcription factors; Cardiogenic differentiation; Epithelial-mesenchymal transition; Long noncoding RNA Braveheart; Mesenchymal stem cells; Mesoderm posterior1