Knockdown of SEMA7A alleviates MPP+‐induced apoptosis and inflammation in BV2 microglia via PPAR‐γ activation and MAPK inactivation

Abstract

The inflammation mediated by microglial cells plays an important role in the process of neurodegenerative diseases. Recent evidence indicates that semaphorin 7A (SEMA7A) is implicated in various neurodegenerative diseases, but whether it plays a role in Parkinson's disease (PD)remains unclear. In this study, 1.0 mmol/L 1-methyl-4-phenylpyridinium (MPP+ )-stimulated mouse microglia (BV2)cells were used as an in vitro model of PD. The expression of SEMA7A was detected by quantitative polymerase chain reaction. Cell Counting Kit-8 and apoptosis kits were used to analyze the viability and apoptosis of BV-2 cells. The content of IL-6, IL-β, and tumor necrosis factor-α was determined by ELISA (enzyme-linked immunosorbent assay) kit. Western blot was used to detect the protein expression level of the inducible NO synthase and cyclooxygenase-2. Our findings indicated that SEMA7A expression in BV2 cells was upregulated after MPP+ stimulation. Knockdown of SEMA7A promoted cell viability while it inhibited apoptosis and the expression of proinflammatory enzymes and proinflammatory cytokines. Silencing SEMA7A-induced peroxisome proliferator-activated receptor-gamma (PPAR-γ) activation and mitogen-activated protein kinase (MAPK)signaling pathway inactivation. Furthermore, a PPAR-γ inhibitor and an MAPK activator promoted the effect of MPP+ on cell viability, apoptosis, and inflammation of BV2 cells; what is more, the PPAR-γinhibitor and MAPK activator blocked the inhibitory effect of SEMA7A downregulation on MPP+ -induced injury. In general, knockdown of SEMA7A inhibits MPP+ -induced BV2 cell apoptosis and inflammation via PPAR-γactivation and MAPK inactivation, which may provide a new therapy target for PD.