Background
Microglia are involved in many neurodegenerative diseases and repairment of traumatic injury to the CNS. Activin A is a neurotrophic and neuroprotective factor that can regulate the activities of macrophages/microglia. However, the effects of activin A on the migration of microglia are still unclear. In this study, the role of activin A in regulation of the microglia migration was investigated with the murine microglial BV2 cell.
Conclusions
These findings revealed that activin A regulated the biological behavior of BV2 cells via Smad3 signaling, suggesting that activin A may serve as a potential treatment target for neuroinflammation and glia scar formation in nervous system.
Methods
The levels of cytokines were detected by enzyme-linked immunosorbent assay (ELISA). The protein expression was examined by Western blotting. The adhesion of BV2 cells was assayed by real-time cell analysis (RTCA). The migration of BV2 cells was determined by transwell chamber and microfluidics device. Smad3 was overexpressed or knocked down in BV2 cells by transfection of Smad3 or Smad3 shRNA-expressing plasmids.
Results
Activin A inhibited the release of nitric oxide (NO) and inflammatory cytokines of TNF-α and IL-6 and the expression of TNF-α and IL-6 mRNA by BV2 cells. In contrast, activin A promoted the production of TGF-β1. Activin A inhibited adhesion, promoted wound healing and migration which is related to the expression of N-cadherin and E-cadherin expression. Additionally, Smad3 overexpression in BV2 cells decreased the levels of TNF-α and IL-6, and promoted the wound healing, whereas Smad3 knockdown showed the opposite effects. Conclusions: These findings revealed that activin A regulated the biological behavior of BV2 cells via Smad3 signaling, suggesting that activin A may serve as a potential treatment target for neuroinflammation and glia scar formation in nervous system.