Basic fibroblast growth factor promotes melanocyte migration via activating PI3K/Akt-Rac1-FAK-JNK and ERK signaling pathways

IUBMB Life. 2016 Sep;68(9):735-47. doi: 10.1002/iub.1531. Epub 2016 Jun 27.

Abstract

Vitiligo is a depigmentation disorder characterized by loss of functional melanocytes of the skin epidermis. The pathogenesis of vitiligo remains elusive. The purpose of this study is to investigate the effects of basic fibroblast growth factor (bFGF) on melanocyte migration, including its biochemical mechanism using transwell assay in vitro. We found that melanocyte treated with bFGF showed a significant increase in migration and cytoskeletal rearrangement. These changes were associated with increased activation of PI3K/Akt, Rac1, FAK, JNK, and ERK. Likewise, reduction of PI3K/Akt, Rac1, FAK, JNK, and ERK activity using selective inhibitors or siRNA was associated with impediment of bFGF-induced melanocyte migration. In addition, activity of Rac1, FAK, and JNK was reduced in cells in which PI3K/Akt was inhibited, activity of FAK and JNK was reduced in cells in which the Rac1 was inhibited, and activity of JNK was reduced in cells in which the FAK was inhibited. Collectively, these data demonstrate that bFGF facilitated melanocyte migration via PI3K/Akt-Rac1-FAK-JNK and ERK signaling pathways. © 2016 IUBMB Life, 68(9):735-747, 2016.

Keywords: Rac-1; basic fibroblast growth factor; melanocytes; migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Movement / drug effects*
  • Cell Movement / genetics
  • Epidermis / drug effects
  • Epidermis / pathology
  • Fibroblast Growth Factor 2 / administration & dosage
  • Fibroblast Growth Factor 2 / genetics*
  • Fibroblast Growth Factor 2 / metabolism
  • Focal Adhesion Kinase 1 / genetics
  • Humans
  • MAP Kinase Kinase 4 / genetics
  • MAP Kinase Signaling System / drug effects
  • Melanocytes / drug effects*
  • Melanocytes / metabolism
  • Melanocytes / pathology
  • Phosphatidylinositol 3-Kinases / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • RNA, Small Interfering / genetics
  • Vitiligo / drug therapy
  • Vitiligo / genetics*
  • Vitiligo / pathology
  • rac1 GTP-Binding Protein / genetics

Substances

  • RAC1 protein, human
  • RNA, Small Interfering
  • Fibroblast Growth Factor 2
  • Phosphatidylinositol 3-Kinases
  • Focal Adhesion Kinase 1
  • PTK2 protein, human
  • Proto-Oncogene Proteins c-akt
  • MAP Kinase Kinase 4
  • rac1 GTP-Binding Protein