title: The influence of TSA and VPA on the in vitro differentiation of bone marrow mesenchymal stem cells into neuronal lineage cells: Gene expression studies.
abstract: BACKGROUND
  Epigenetic mechanisms regulate the transcription of genes, which can affect the differentiation of MSCs. The aim of the current work is to determine how the histone deacetylase inhibitors TSA and VPA affect the expression of neuronal lineage genes in a culture of rat MSCs (rMSCs).
  
  
  METHODS
  We analyzed the expression of early neuron marker gene (Tubb3), mature neuron markers genes (Vacht, Th, Htr2a) and the oligodendrocyte progenitor marker gene (GalC). Moreover, changes in the gene expression after three different periods of exposure to TSA and VPA were investigated for the first time.
  
  
  RESULTS
  After six days of exposition to TSA and VPA, the expression of Tubb3 and GalC decreased, while the expression of Th increased. The highest increase of VAChT expression was observed after three days of TSA and VPA treatment. A decrease in Htr2a gene expression was observed after TSA treatment and an increase was observed after VPA treatment. We also observed that TSA and VPA inhibited cell proliferation and the formation of neurospheres in the rMSCs culture.
  
  
  CONCLUSIONS
  The central findings of our study are that TSA and VPA affect the expression of neuronal lineage genes in an rMSCs culture. After exposure to TSA or VPA, the expression of early neuronal gene decreases but equally the expression of mature neuron genes increases. After TSA and VPA treatment ER of the oligodendrocyte progenitor marker decreased. TSA and VPA inhibit cell proliferation and the formation of neurospheres in rMSCs culture.
authors.affiliation: Department of Medical Genetics, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Sosnowiec, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Fila-Danilow
authors.affiliation: Department of Medical Genetics, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Sosnowiec, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Borkowska
authors.affiliation: Department of Medical Genetics, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Sosnowiec, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Paul-Samojedny
authors.affiliation: Department of Medical Genetics, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Sosnowiec, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kowalczyk
authors.affiliation: Department of Medical Genetics, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Sosnowiec, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Kowalski
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D058953:Neural Stem Cells / Q000187:drug effects*; D009474:Neurons / Q000378:metabolism; D051381:Rats; D014404:Tubulin / Q000378:metabolism*; D014635:Valproic Acid / Q000493:pharmacokinetics*
chemical_list: D056572:Histone Deacetylase Inhibitors; D014404:Tubulin; D014635:Valproic Acid