KLF2 protects BV2 microglial cells against oxygen and glucose deprivation injury by modulating BDNF/TrkB pathway.

Cerebral ischemia injury is common in cerebral ischemic disease, and treatment options remain limited. Krueppel-like factor 2 (KLF2) is reported to negatively regulate inflammation in several ischemic diseases. Our study aimed to investigate the effects and underlying mechanism of KLF2 in BV2 microglial cells exposed to oxygen and glucose deprivation (OGD). We first found decreased KLF2 and toll-like receptor 2 (TLR2)/TLR4 in these cells. OGD also led to decrease in cell viability and increase in LDH release, apoptosis, the Bax/Bcl-2 ratio, and caspase3/9 expression, as well as production of inflammatory cytokines (e.g., TNFα, IL-1β and IL-6), reactive oxygen species (ROS), and TLR2/TLR4. To examine KLF2's effects on these OGD effects, we infected BV2 microglial cells with an ad-KLF2 or negative control vector, and we found that KLF2 reversed all of the effects of OGD exposure. Furthermore, KLF2 significantly increased levels of BDNF and TrkB in these cells, but these effects were blocked by K252a, a BDNF/TrkB inhibitor. K252a also decreased cell viability and increased apoptosis, inflammatory factors, ROS production, and TLR2/TLR4 expression in OGD-exposed BV2 cells that were treated with KLF2, were implying that K252a could reverse the effects of KLF2 on these cells. Taken together, our study results indicate that KLF2 may protect BV2 microglial cells against OGD injury by activating the BDNF/TrkB pathway.