title: Brain derived neurotrophic factor contributes to the cardiogenic potential of adult resident progenitor cells in failing murine heart.
abstract: OBJECTIVE
  Resident cardiac progenitor cells show homing properties when injected into the injured but not to the healthy myocardium. The molecular background behind this difference in behavior needs to be studied to elucidate how adult progenitor cells can restore cardiac function of the damaged myocardium. Since the brain derived neurotrophic factor (BDNF) moderates cardioprotection in injured hearts, we focused on delineating its regulatory role in the damaged myocardium.
  
  
  RESULTS
  Comparative gene expression profiling of freshly isolated undifferentiated Sca-1 progenitor cells derived either from heart failure transgenic αMHC-CyclinT1/Gαq overexpressing mice or wildtype littermates revealed transcriptional variations. Bdnf expression was up regulated 5-fold during heart failure which was verified by qRT-PCR and confirmed at protein level. The migratory capacity of Sca-1 cells from transgenic hearts was improved by 15% in the presence of 25 ng/ml BDNF. Furthermore, BDNF-mediated effects on Sca-1 cells were studied via pulsed Stable Isotope Labeling of Amino acids in Cell Culture (pSILAC) proteomics approach. After BDNF treatment significant differences between newly synthesized proteins in Sca-1 cells from control and transgenic hearts were observed for CDK1, SRRT, HDGF, and MAP2K3 which are known to regulate cell cycle, survival and differentiation. Moreover BDNF repressed the proliferation of Sca-1 cells from transgenic hearts.
  
  
  CONCLUSIONS
  Comparative profiling of resident Sca-1 cells revealed elevated BDNF levels in the failing heart. Exogenous BDNF (i) stimulated migration, which might improve the homing ability of Sca-1 cells derived from the failing heart and (ii) repressed the cell cycle progression suggesting its potency to ameliorate heart failure.
authors: Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany; Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
authors: Rasmita
authors: R
authors: Samal
authors: Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
authors: Sabine
authors: S
authors: Ameling
authors: Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
authors: Vishnu
authors: V
authors: Dhople
authors: Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
authors: Praveen Kumar
authors: PK
authors: Sappa
authors: Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany; DZHK (German Center for Cardiovascular Research) partner site, Greifswald, Germany.
authors: Kristin
authors: K
authors: Wenzel
authors: Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany; DZHK (German Center for Cardiovascular Research) partner site, Greifswald, Germany.
authors: Uwe
authors: U
authors: Völker
authors: Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany; DZHK (German Center for Cardiovascular Research) partner site, Greifswald, Germany.
authors: Stephan B
authors: SB
authors: Felix
authors: Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany; DZHK (German Center for Cardiovascular Research) partner site, Greifswald, Germany.
authors: Elke
authors: E
authors: Hammer
authors: Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany; DZHK (German Center for Cardiovascular Research) partner site, Greifswald, Germany.
authors: Stephanie
authors: S
authors: Könemann
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D006333:Heart Failure / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism / Q000502:physiology
chemical_list: D000950:Antigens, Ly; D019208:Brain-Derived Neurotrophic Factor; C074650:Ly6a protein, mouse; D008565:Membrane Proteins