Reduction of TRPV1 expression on neurons due to downregulation of P2X7R in neonatal rat dorsal root ganglion satellite glial cells under co-culture conditions

Background information: The purinergic ligand-gated ion channel 7 receptor (P2X7R) is an ATP-gated ion channel that transmits extracellular signals and induces corresponding biological effects, transient receptor potential vanilloid type 1 (TRPV1) is a non-selective cation channel that maintains normal physiological functions; numerous studies showed that P2X7R and TRPV1 are associated with inflammatory reactions. Results: The effect of P2X7R knockdown in satellite glial cells (SGCs) on neuronal TRPV1 expression under high glucose and high free fat (HGHF) environment was investigated. P2X7 short hairpin RNA (shRNA) was utilized to downregulate P2X7R in SGCs, and treated and untreated SGCs were co-cultured with neuronal cell lines. The expression levels of inflammatory factors and signaling pathways in SGCs and neurons were measured using Western blot analysis, RT-qPCR, immunofluorescence, and enzyme-linked immunosorbent assays. Results suggested that P2X7 shRNA reduced the expression levels of P2X7R protein and mRNA in SGCs surrounding DRG neurons and downregulated the release of tumor necrosis factor-alpha and interleukin-1 beta via the Ca2+/p38 MAPK/NF-kappa B pathway. Additionally, the downregulation of P2X7R might decrease TRPV1 expression in neurons via the Ca2+/PKC-epsilon/p38 MAPK pathway.Conclusions: Reducing P2X7R expression in SCGs in an HGHF environment could decrease neuronal TRPV1 expression via the Ca2+/PKC-epsilon/p38 MAPK pathway. Reduction of TRPV1 expression in neurons and its possible transduction mechanism due to downregulation of P2X7R in satellite glial cells. Satellite glial cells were activated by high-glucose and high-free fat, inducing the upregulation of P2X7R, which increases the release of inflammatory factors via the Ca2+/P38 MAPK/NF-kappa B signaling pathway. The released inflammatory factors acted on neurons and upregulated neuronal TRPV1 expression via Ca2+/ PKC-epsilon / P38 MAPK signaling pathway, while knockdown of P2X7R with P2X7 shRNA might downregulate TRPV1 expression on neurons. image