ABSTRACT
OBJECTIVE: To explore the effect of nuclear factor erythroid 2-related factor 2 (Nrf 2) on microglial inflammatory response and proliferation after spinal cord injury (SCI) through the glyceraldehyde phosphate dehydrogenase (GAPDH) / Seven in absentia homolog 1 (Siah 1) signaling pathway. METHODS: Human microglia HMC3 was induced by lipopolysaccharide (LPS) to establish a SCI cell model. Microglia morphology after LPS stimulation was observed by transmission electron microscope (TEM), and cellular Nrf2, GAPDH/Siah1 pathway expression and cell viability were determined. Subsequently, the Nrf2 overexpression plasmid was transfected into microglia to observe changes in cell viability and GAPDH/Siah1 pathway expression. RESULTS: Microglia, mostly amoeba-like, were found to have enlarged cell bodies after LPS stimulation, with an increased number of cell branches, highly expressed Nrf2, GAPDH and Siah1, and decreased cell viability (P<0.05). Up-regulating Nrf2 inhibited the GAPDH/Siah1 axis, decreased inflammatory responses, and enhanced activity in post-SCI microglia (P<0.05). CONCLUSION: Up-regulating Nrf2 expression can reverse the inflammatory reaction of microglia after LPS stimulation and enhance their activity by inhibiting the GAPDH/Siah1 axis.
ABSTRACT
Osteoporosis is a progressive bone disorder with a higher incidence in the elderly and has become a major public health concern all over the world. Therefore, it is urgent to investigate the mechanisms underlying the pathogenesis of osteoporosis. In this study, the osteoporosis animal model was established, and then rat bone marrow mesenchymal stem cells (rBMSCs) were cultured. The results showed that PHF8 expression was decreased in osteoporosis rats compared to controls. Overexpression of PHF8 promoted BMSC osteogenic differentiation and the expression of osteogenesis-related genes. In addition, the Wnt/ß-catenin signaling pathway in BMSCs was inhibited in osteoporosis rats, which was rescued by overexpression of PHF8. After treatment with the Wnt pathway antagonist, the improved osteogenic differentiation of BMSCs induced by overexpression of PHF8 was blocked. Collectively, our data revealed that the decreased expression of PHF8 in osteoporosis rats suppressed the osteogenic differentiation of BMSCs, which was then restored by PHF8 overexpression. Furthermore, the inhibition of the Wnt/ß-catenin signaling pathway in BMSCs suppressed osteogenic differentiation. Thus, these findings indicated that PHF8 plays a role in osteogenic differentiation through the Wnt/ß-catenin signaling pathway.
ABSTRACT
BACKGROUND: Spinal cord injury (SCI) remains a huge medical problem nowadays as there is no hospital providing the versatile strategies for repairing central nervous system and restoring function. Herein, we focused on PC-12 cells as an important research tool and studied the potential role of resveratrol (RSV) in inflammation induced by LPS. RESULTS: RSV improved inflammatory injury and functional recovery in rat model of SCI. RSV inhibited LPS-induced inflammatory injury in PC-12 cells via increasing viability, decreasing apoptosis, and suppressing IL-1ß, IL-6, and TNF-α expression. miR-132 was down-regulated after LPS treatment but up-regulated after RSV administration. miR-132 silence curbed the protective effect of RSV. The results including increase of cell growth, suppression of inflammatory response, and blocking of NF-κB and p38MAPK pathways produced by RSV were all reversed by miR-132 silence. CONCLUSION: RSV could up-regulate miR-132 and further ameliorate inflammatory response in PC-12 cells by inhibiting NF-κB and p38MAPK pathways.
