title: GATA-4 induces changes in electrophysiological properties of rat mesenchymal stem cells.
abstract: BACKGROUND
  Transplanted mesenchymal stem cells (MSC) can differentiate into cardiac cells that have the potential to contribute to heart repair following ischemic injury. Overexpression of GATA-4 can significantly increase differentiation of MSC into cardiomyocytes (CM). However, the specific impact of GATA-4 overexpression on the electrophysiological properties of MSC-derived CM has not been well documented.
  
  
  METHODS
  Adult rat bone marrow MSC were retrovirally transduced with GATA-4 (MSC(GATA-4)) and GFP (MSC(Null)) and subsequently co-cultured with neonatal rat ventricular cardiomyocytes (CM). Electrophysiological properties and mRNA levels of ion channels were assessed in MSC using patch-clamp technology and real-time PCR.
  
  
  RESULTS
  MSC(GATA-4) exhibited higher levels of the TTX-sensitive Na(+) current (INa.TTX), L-type calcium current (ICa.L), transient outward K(+) current (Ito), delayed rectifier K(+) current (IKDR) and inwardly rectifying K(+) current (IK1) channel activities reflective of electrophysiological characteristics of CM. Real-time PCR analyses showed that MSC(GATA-4) exhibited upregulated mRNA levels of Kv1.2, Kv2.1, SCN2a1, CCHL2a, KV1.4 and Kir1.1 channels versus MSC(Null). Interestingly, MSC(GATA-4) treated with IGF-1 neutralizing antibodies resulted in a significant decrease in Kir1.1, Kv2.1, KV1.4, CCHL2a and SCN2a1 channel mRNA expression. Similarly, MSC(GATA-4) treated with VEGF neutralizing antibodies also resulted in an attenuated expression of Kv2.1, Kv1.2, Kv1.4, Kir1.1, CCHL2a and SCN2a1 channel mRNAs.
  
  
  CONCLUSIONS
  GATA-4 overexpression increases Ito, IKDR, IK1, INa.TTX and ICa.L currents in MSC. Cytokine (VGEF and IGF-1) release from GATA-4 overexpressing MSC can partially account for the upregulated ion channel mRNA expression.
  
  
  CONCLUSIONS
  Our results highlight the ability of GATA4 to boost the cardiac electrophysiological potential of MSC.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Li
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
authors.forename: Ya-Feng
authors.initials: YF
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
authors.forename: Ting-Bo
authors.initials: TB
authors.lastname: Jiang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China. Electronic address: yxjdemail@126.com.
authors.forename: Xiang-Jun
authors.initials: XJ
authors.lastname: Yang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
authors.forename: Wen-Ping
authors.initials: WP
authors.lastname: Jiang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D050991:GATA4 Transcription Factor / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
chemical_list: D016207:Cytokines; D050991:GATA4 Transcription Factor; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I
keywords: Electrophysiological property; GATA-4; Ion channel; Mesenchymal stem cell; Patch clamp; Transdifferentiation