PMID- 23006419
OWN - NLM
STAT- MEDLINE
DCOM- 20140127
LR  - 20220211
IS  - 1998-3654 (Electronic)
IS  - 0019-5359 (Linking)
VI  - 64
IP  - 9
DP  - 2010 Sep
TI  - The mechanism underlying the differentiation of human umbilical cord-derived 
      mesenchymal stem cells into myocardial cells induced by 5-azacytidine.
PG  - 402-7
AB  - OBJECTIVE: To investigate the molecular mechanism underlying the differentiation 
      of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) into myocardial 
      cells induced by 5-azacytidine (5-aza), and to explore the expression and 
      significance of DLL4-Notch signaling in this process. MATERIALS AND METHODS: 
      hUCMSCs were isolated and purified from the umbilical cords of normal or cesarean 
      term deliveries under sterile conditions. After treatment with 5-aza for 24 h, 
      hUCMSCs was continued to culture, the expression of GATA4 and NKx2.5 at 4 weeks 
      after induction, DLL4 and Notch1 mRNA at 1d, 3d, 5d, 7d after induction were 
      detected. The expression of cardiac troponin I (cTnI) after 4 weeks was 
      determined by immunocytochemistry. RESULTS: hUCMSCs treated with 5-aza were 
      stained positively for cTnI 4 weeks after induction. The expression of Notch1 and 
      DLL4 mRNA in the 5-aza-induced group was stable and significantly higher than 
      that in the control group (mean Ct value for the Notch1 gene: 0.51 +/- 0.21 in the 
      5-aza-induced group vs. 7.85 +/- 0.35 in the control group; mean Ct value for the 
      DLL4 gene: 1.60 +/- 0.49 in the 5-aza-induced group vs. 12.42 +/- 0.73 in the control 
      group). Similar results were observed for Nkx2.5 and GATA4 genes. The expressions 
      of Nkx2.5 and GATA4 mRNA in the 5-aza group were 4.72 +/- 0.58 and 3.76 +/- 0.06 
      times higher than that in the control group, respectively, with statistical 
      significance. CONCLUSIONS: hUCMSCs can be differentiated into myocardial cells by 
      5-aza induction in vitro. 5-Aza may affect this process by regulating the 
      expression of GATA4 and Nkx2.5 genes. The DLL4-Notch signal pathway may be 
      involved in this process.
FAU - Ruan, Zhong-Bao
AU  - Ruan ZB
AD  - Department of Cardiology, Taizhou People's Hospital, Taizhou-225300, P.R. China. 
      ruanzhongbao@medmail.com.cn
FAU - Zhu, Li
AU  - Zhu L
FAU - Yin, Yi-Gang
AU  - Yin YG
FAU - Chen, Ge-Cai
AU  - Chen GC
LA  - eng
PT  - Journal Article
PL  - India
TA  - Indian J Med Sci
JT  - Indian journal of medical sciences
JID - 0373023
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (DLL4 protein, human)
RN  - 0 (GATA4 Transcription Factor)
RN  - 0 (GATA4 protein, human)
RN  - 0 (Homeobox Protein Nkx-2.5)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (NKX2-5 protein, human)
RN  - 0 (NOTCH1 protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptor, Notch1)
RN  - 0 (Transcription Factors)
RN  - 0 (Troponin I)
RN  - M801H13NRU (Azacitidine)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Azacitidine/*pharmacology
MH  - Calcium-Binding Proteins
MH  - Cell Differentiation/*drug effects
MH  - Cells, Cultured
MH  - Fetal Blood/cytology
MH  - GATA4 Transcription Factor/genetics
MH  - Gene Expression/drug effects
MH  - Homeobox Protein Nkx-2.5
MH  - Homeodomain Proteins/genetics
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/genetics
MH  - Mesenchymal Stem Cells/*cytology/metabolism
MH  - Myocytes, Cardiac/*cytology/metabolism
MH  - RNA, Messenger/metabolism
MH  - Receptor, Notch1/genetics
MH  - Signal Transduction/drug effects
MH  - Transcription Factors/genetics
MH  - Troponin I/metabolism
EDAT- 2010/09/01 00:00
MHDA- 2014/01/28 06:00
CRDT- 2012/09/26 06:00
PHST- 2012/09/26 06:00 [entrez]
PHST- 2010/09/01 00:00 [pubmed]
PHST- 2014/01/28 06:00 [medline]
AID - IndianJMedSci_2010_64_9_402_101176 [pii]
PST - ppublish
SO  - Indian J Med Sci. 2010 Sep;64(9):402-7.