GDF11 Regulates M1 and M2 Polarization of BV2 Microglial Cells via p38 MAPK Signaling Pathway.

Abstract

Growth differentiation factor 11 (GDF11), a member of the transforming growth factor β (TGF-β) superfamily, exhibits great neurological and mental diseases modulating potential. However, its specific effects on microglia, which are the primary immune cells of the nervous system, remain unclear. To investigate the mechanism by which GDF11 affects BV2 microglial cells in vitro and to elucidate its regulatory mechanisms, we carried out a systematic examination of how GDF11 affects the various functions of lipopolysaccharide (LPS)-induced BV2 microglial cells and found that endogenous GDF11 could significantly inhibit cell proliferation, apoptosis, and migration. Specifically, GDF11 inhibited the polarization of BV2 cells to the proinflammatory M1 phenotype and promoted their polarization to the anti-inflammatory M2 phenotype, precipitating a reduction in the expression of CD86 and nitric oxide synthase 2 (NOS2), and an increase in the expression of CD206 and arginase-1. Additionally, RNA-seq and Western blotting experiments revealed that GDF11 activated the p38 MAPK (mitogen-activated protein kinase) pathway, mediating its effects on BV2 cells. Taken together, GDF11 could crucially regulate microglial responses and promote an anti-inflammatory microglial phenotype through the p38 MAPK signaling axis, which may have potential therapeutic implications in neuroinflammatory diseases.