Spatiotemporal expression of FOXA1 correlates with reactive gliosis after spinal cord injury

Neuropeptides. 2017 Dec:66:36-44. doi: 10.1016/j.npep.2017.08.002. Epub 2017 Aug 18.

Abstract

Forkhead box A1 (FOXA1) is a member of the FOX family of transcription factors and involved in various mammalian processes. However, the expression and function of FOXA1 in central nervous system (CNS) are still with limited acquaintance. In present study, we performed an acute spinal cord injury (SCI) model in adult rats and investigated the dynamic changes of FOXA1 expression in spinal cord. We found that FOXA1 protein levels were significantly increased after SCI and we observed that the expression of FOXA1 is enhanced in the white matter. Meanwhile, double immunofluorescence staining showed that increased levels of FOXA1 were striking in astrocytes and microglia. We also examined the expression of proliferating cell nuclear antigen (PCNA), whose changes were correlated with the expression profiles of FOXA1. In vitro, FOXA1 depletion by siRNA inhibited astrocyte proliferation and migration. Meanwhile, FOXA1 knockdown also reduce cell cycle related proteins. Which indicated that FOXA1 might modulate cell cycle progression and play a crucial role in cell proliferation. Furthermore, FOXA1 knockdown also inhibited LPS-induced synthesis/secretion of IL-1β and TNF-α in primary microglia. These results indicated that FOXA1 might play an important role in pathophysiology after SCI.

Keywords: Cell cycle; FOXA1; Inflammation; Proliferation; Spinal cord injury.

MeSH terms

  • Animals
  • Astrocytes / metabolism*
  • Astrocytes / pathology
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Gliosis / etiology
  • Gliosis / metabolism*
  • Gliosis / pathology
  • Hepatocyte Nuclear Factor 3-alpha / metabolism*
  • Male
  • Microglia / metabolism*
  • Microglia / pathology
  • Neurons / metabolism
  • Neurons / pathology
  • Proliferating Cell Nuclear Antigen / metabolism
  • RNA, Small Interfering
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Spinal Cord Injuries / complications
  • Spinal Cord Injuries / metabolism*
  • Spinal Cord Injuries / pathology

Substances

  • Foxa1 protein, rat
  • Hepatocyte Nuclear Factor 3-alpha
  • Proliferating Cell Nuclear Antigen
  • RNA, Small Interfering