Annexin-1 Mediates Microglial Activation and Migration via the CK2 Pathway during Oxygen–Glucose Deprivation/Reperfusion

Abstract

Annexin-1 (ANXA1) has shown neuroprotective effects and microglia play significant roles during central nervous system injury, yet the underlying mechanisms remain unclear. This study sought to determine whether ANXA1 regulates microglial response to oxygen–glucose deprivation/reperfusion (OGD/R) treatment and to clarify the downstream molecular mechanism. In rat hippocampal slices, OGD/R treatment enhanced the ANXA1 expression in neuron, the formyl peptide receptor (FPRs) expression in microglia, and the microglial activation in the CA1 region (cornu ammonis 1). These effects were reversed by the FPRs antagonist Boc1. The cell membrane currents amplitude of BV-2 microglia (the microglial like cell-line) was increased when treated with Ac2-26, the N-terminal peptide of ANXA1. Ac2-26 treatment enhanced BV-2 microglial migration whereas Boc1 treatment inhibited the migration. In BV-2 microglia, both the expression of the CK2 target phosphorylated α-E-catenin and the binding of casein kinase II (CK2) with α-E-catenin were elevated by Ac2-26, these effects were counteracted by the CK2 inhibitor TBB and small interfering (si) RNA directed against transcripts of CK2 and FPRs. Moreover, both TBB and siRNA-mediated inhibition of CK2 blocked Ac2-26-mediated BV-2 microglia migration. Our findings indicate that ANXA1 promotes microglial activation and migration during OGD/R via FPRs, and CK2 target α-E-catenin phosphorylation is involved in this process.

Connections of annexin A1 and translocator protein-18 kDa on toll like receptor stimulated BV-2 cells

“…The role of ANXA1 to inhibit and induce the secretion of pro-inflammatory and anti-inflammatory cytokines, respectively, has been fully described in different cells [46,47]. In fact, ANXA1 treatment reduced the elevated concentration of IL-6, TNFα and IL-4 in BV2 cells stimulated by synthetic amyloid peptide Aβ 1-42 [36], and the treatment of rat primary culture microglia with Ac2-26 reduced the LPS-induced secretion of IL1β and TNFα [48]. Here we confirm the anti-inflammatory profile elicited by exogenous ANXA1, since it elicited a reduction on LPS-induced TNFα and IL1β over secretion in BV2 cells.…”

ANXA1 directs Schwann cells proliferation and migration to accelerate nerve regeneration through the FPR2/AMPK pathway

“…10 Another study reported that during oxygen-glucose deprivation, ANXA1 promoted microglial activation and migration. 11 We therefore determined whether exogeneous ANXA1-induced SC cellular proliferation and migration, thus, leading to nerve regeneration.…”

Tumoral ANXA1 Is a Predictive Marker for Sunitinib Treatment of Renal Cancer Patients

“…The neuroprotective effect of ANXA1 was explored and the findings indicate that ANXA1 promotes microglial activation and migration 38 .…”