Valproic Acid Promotes Early Neural Differentiation in Adult Mesenchymal Stem Cells Through Protein Signalling Pathways

Cells. 2020 Mar 4;9(3):619. doi: 10.3390/cells9030619.

Abstract

Regenerative medicine is a rapidly expanding area in research and clinical applications. Therapies involving the use of small molecule chemicals aim to simplify the creation of specific drugs for clinical applications. Adult mesenchymal stem cells have recently shown the capacity to differentiate into several cell types applicable for regenerative medicine (specifically neural cells, using chemicals). Valproic acid was an ideal candidate due to its clinical stability. It has been implicated in the induction of neural differentiation; however, the mechanism and the downstream events were not known. In this study, we showed that using valproic acid on adult mesenchymal stem cells induced neural differentiation within 24 h by upregulating the expression of suppressor of cytokine signaling 5 (SOCS5) and Fibroblast growth factor 21 (FGF21), without increasing the potential death rate of the cells. Through this, the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway is downregulated, and the mitogen-activated protein kinase (MAPK) cascade is activated. The bioinformatics analyses revealed the expression of several neuro-specific proteins as well as a range of functional and structural proteins involved in the formation and development of the neural cells.

Keywords: JAK/STAT pathway; MAPK pathway; adipose derived stem cells; protein interactions; valproic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / drug effects*
  • DNA-Binding Proteins / drug effects*
  • DNA-Binding Proteins / metabolism
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / metabolism
  • Protein-Tyrosine Kinases / drug effects
  • Protein-Tyrosine Kinases / metabolism
  • Trans-Activators / drug effects
  • Trans-Activators / metabolism
  • Valproic Acid / pharmacology*

Substances

  • DNA-Binding Proteins
  • Trans-Activators
  • Valproic Acid
  • Protein-Tyrosine Kinases