PMID- 25967873
OWN - NLM
STAT- MEDLINE
DCOM- 20160208
LR  - 20190212
IS  - 1421-9778 (Electronic)
IS  - 1015-8987 (Linking)
VI  - 35
IP  - 6
DP  - 2015
TI  - Effects of synthetic neural adhesion molecule mimetic peptides and related 
      proteins on the cardiomyogenic differentiation of mouse embryonic stem cells.
PG  - 2437-50
LID - 10.1159/000374044 [doi]
AB  - BACKGROUND/AIMS: Pluripotent stem cells differentiating into cardiomyocyte-like 
      cells in an appropriate cellular environment have attracted significant 
      attention, given the potential use of such cells for regenerative medicine. 
      However, the precise mechanisms of lineage specification of pluripotent stem 
      cells are still largely to be explored. Identifying the role of various small 
      synthetic peptides involved in cardiomyogenesis may provide new insights into 
      pathways promoting cardiomyogenesis. METHODS: In the present study, using a 
      transgenic murine embryonic stem (ES) cell lineage expressing enhanced green 
      fluorescent protein (EGFP) under the control of alpha-myosin heavy chain (alpha-MHC) 
      promoter (palphaMHC-EGFP), we investigated the cardiomyogenic effects of 7 synthetic 
      peptides (Betrofin3, FGLs, FGL(L), hNgf_C2, EnkaminE, Plannexin and C3) on 
      cardiac differentiation. The expression of several cardiac-specific markers was 
      determined by RT-PCR whereas the structural and functional properties of derived 
      cardiomyocytes were examined by immunofluorescence and electrophysiology, 
      respectively. RESULTS: The results revealed that Betrofin3, an agonist of brain 
      derived neurotrophic factor (BDNF) peptide exerted the most striking 
      pro-cardiomyogenic effect on ES cells. We found that BDNF receptor, TrkB 
      expression was up-regulated during differentiation. Treatment of differentiating 
      cells with Betrofin3 between days 3 and 5 enhanced the expression of 
      cardiac-specific markers and improved cardiomyocyte differentiation and 
      functionality as revealed by genes regulation, flow cytometry and patch clamp 
      analysis. Thus Betrofin3 may exert its cardiomyogenic effects on ES cells via 
      TrkB receptor. CONCLUSION: Taken together, the results suggest that Betrofin3 
      modulates BDNF signaling with positive cardiomyogenic effect in stage and 
      dose-dependent manner providing an effective strategy to increase ES cell-based 
      generation of cardiomyocytes and offer a novel therapeutic approach to cardiac 
      pathologies where BDNF levels are impaired.
CI  - (c) 2015 S. Karger AG, Basel.
FAU - Xu, Ruodan
AU  - Xu R
AD  - ENKAM Pharmaceuticals A/S, Copenhagen, Denmark.
FAU - Srinivasan, Sureshkumar Perumal
AU  - Srinivasan SP
FAU - Sureshkumar, Poornima
AU  - Sureshkumar P
FAU - Nembo, Erastus Nembu
AU  - Nembo EN
FAU - Schafer, Christoph
AU  - Schafer C
FAU - Semmler, Judith
AU  - Semmler J
FAU - Matzkies, Matthias
AU  - Matzkies M
FAU - Albrechtsen, Morten
AU  - Albrechtsen M
FAU - Hescheler, Jurgen
AU  - Hescheler J
FAU - Nguemo, Filomain
AU  - Nguemo F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150424
PL  - Germany
TA  - Cell Physiol Biochem
JT  - Cellular physiology and biochemistry : international journal of experimental 
      cellular physiology, biochemistry, and pharmacology
JID - 9113221
RN  - 0 (Betrofin 3)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Dendrimers)
RN  - 0 (Myh6 protein, mouse)
RN  - 0 (Neural Cell Adhesion Molecules)
RN  - 0 (Oligopeptides)
RN  - 0 (Peptides)
RN  - 0 (enhanced green fluorescent protein)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 3.6.4.1 (Myosin Heavy Chains)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cell Differentiation/*drug effects
MH  - Cell Line
MH  - Dendrimers/metabolism
MH  - Gene Expression Regulation/drug effects
MH  - Green Fluorescent Proteins/metabolism
MH  - Mice
MH  - Mouse Embryonic Stem Cells/*drug effects/metabolism
MH  - Myocytes, Cardiac/*drug effects/metabolism
MH  - Myosin Heavy Chains/metabolism
MH  - Neural Cell Adhesion Molecules/*pharmacology
MH  - Oligopeptides/metabolism
MH  - Peptides/*metabolism
MH  - Promoter Regions, Genetic/drug effects
MH  - Receptor, trkB/metabolism
MH  - Signal Transduction/drug effects
EDAT- 2015/05/15 06:00
MHDA- 2016/02/09 06:00
CRDT- 2015/05/14 06:00
PHST- 2015/03/13 00:00 [accepted]
PHST- 2015/05/14 06:00 [entrez]
PHST- 2015/05/15 06:00 [pubmed]
PHST- 2016/02/09 06:00 [medline]
AID - 000374044 [pii]
AID - 10.1159/000374044 [doi]
PST - ppublish
SO  - Cell Physiol Biochem. 2015;35(6):2437-50. doi: 10.1159/000374044. Epub 2015 Apr 
      24.