Mesenchymal stem cells overexpressing neuropeptide S promote the recovery of rats with spinal cord injury by activating the PI3K/AKT/GSK3β signaling pathway
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE280779 | GEO | 2025/02/19
REPOSITORIES: GEO
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Project description:BackgroundTransplantation of nasal mucosa-derived mesenchymal stem cells (EMSCs) overexpressing neuropeptide S (NPS) is a promising approach for treating spinal cord injury (SCI). Despite the potential of stem cell therapy, challenges remain regarding cell survival and differentiation control. We aimed to conduct orthotopic transplantation of transected spinal cord to treat rats with complete SCI.MethodsIn this study, we loaded NPS-overexpressing EMSCs onto hydrogels to enhance cell survival in vivo and promote neuronal differentiation both in vitro and in vivo. However, in vitro co-culture promoted greater neuronal differentiation of neural stem cells (P < 0.01). When transplanted in vivo, NPS-overexpressing EMSCs showed greater cell survival in the transplanted area compared with stem cells without gene modification within 4 weeks after spinal cord implantation in rats (P < 0.01).ResultsCompared with those in the other groups, stable overexpression of NPS-EMSCs in a rat model with SCI significantly improved the treatment effect, reduced glial scar formation, promoted neural regeneration and endogenous neural stem cell proliferation and differentiation into neurons, and improved motor function.ConclusionsThese results indicate that this effect may be achieved by the overexpression of NPS-EMSCs through the activation of the PI3K/Akt/GSK3β signaling pathway. Overall, the overexpression of EMSCs significantly improved the therapeutic effect of SCI in rats, strongly supporting the potential for gene modification of mesenchymal stem cells in clinical applications.
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Project description:Mesenchymal stem cells overexpressing neuropeptide S promote the recovery of rats with spinal cord injury by activating the PI3K/AKT/GSK3β signaling pathway
| PRJNA1180524 | ENA
Project description:Approximately 10% of bone fractures do not heal satisfactorily, leading to significant clinical and socioeconomic implications. Recently, the role of macrophages in regulating bone marrow stem cell (BMSC) differentiation through the osteogenic pathway during fracture healing has attracted much attention. Methods: The tibial monocortical defect model was employed to determine the critical role of macrophage scavenger receptor 1 (MSR1) during intramembranous ossification (IO) in vivo. The potential functions and mechanisms of MSR1 were explored in a co-culture system of bone marrow-derived macrophages (BMDMs), RAW264.7 cells, and BMSCs using qPCR, Western blotting, immunofluorescence, and RNA sequencing. Results: In this study, using the tibial monocortical defect model, we observed delayed IO in MSR1 knockout (KO) mice compared to MSR1 wild-type (WT) mice. Furthermore, macrophage MSR1 mediated PI3K/AKT/GSK3β/β-catenin signaling increased ability to promote osteogenic differentiation of BMSCs in the co-culture system. We also identified proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) as the target gene for macrophage MSR1-activated PI3K/AKT/GSK3β/β-catenin pathway in the co-culture system that facilitated M2-like polarization by enhancing mitochondrial oxidative phosphorylation. Conclusion: Our findings revealed a previously unrecognized function of MSR1 in macrophages during fracture repair. Targeting MSR1 might, therefore, be a new therapeutic strategy for fracture repair.
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Project description:BackgroundClinically, the median survival in patients with metastatic renal cell carcinoma (RCC) was only 6-12 months and a 5-year survival rate of less than 20%. Therefore, an in-depth study of the molecular mechanisms involved in RCC is of great significance for improving the survival of patients with advanced RCC. Acylglycerol kinase (AGK) is a newly discovered lipid kinase that has been reported to be a potent oncogene that may be involved in the regulation of malignant progression in a variety of tumours. However, the expression and biological characteristics of the AGK gene in RCC remain unclear.MethodsAGK expression was quantified by quantitative real-time PCR, Western blotting and immunohistochemistry in RCC cell lines and paired patient tissues. Kaplan-Meier method and Cox proportional hazards models were used to evaluate the prognostic value of AGK in human RCC tissue samples. Chi-squared test was performed to analyse the correlation between AGK expression and the clinicopathological features. Stable overexpression and knockdown of AGK in RCC cells was constructed with lentivirus. The oncogenic effects of AGK in human RCC progression were investigated using assays of colony formation, anchorage-independent growth, EdU assay, cell cycle analysis, wound-healing, trans-well analysis and xenograft tumour model. GSEA and KEGG analysis were conducted to detect the potential pathway of AGK involved in RCC. These results were further confirmed using the luciferase reporter assays, immunofluorescence and in vivo experiments.ResultsAGK expression is significantly elevated in RCC and closely related to the malignant development and poor prognosis in RCC patients. By in vitro and in vivo experiments, AGK was shown to enhance the proliferation of RCC cells by promoting the transition from the G1 phase to the S phase in the cell cycle and to enhance the migration and invasion by promoting epithelial-mesenchymal transition. By activating the PI3K/AKT/GSK3β signalling pathway in RCC, AGK can increase nuclear accumulation of β-catenin, which further upregulated TCF/LEF transcription factor activity.ConclusionsAGK promotes the progression of RCC via activating the PI3K/AKT/GSK3β signalling pathway and might be a potential target for the further research of RCC.
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Project description:Neuroinflammation plays a crucial role in the secondary phase of spinal cord injury (SCI), and is initiated following the activation of toll-like receptor 4 (TLR4). However, the downstream mechanism remains unknown. Pyroptosis is a form of inflammatory programmed cell death, which is closely involved in neuroinflammation, and it can be regulated by TLR4 according to a recent research. In addition, several studies have shown that long non-coding RNAs (lncRNAs) based mechanisms were related to signal transduction downstream of TLR4 in the regulation of inflammation. Thus, in this study, we want to determine whether TLR4 can regulate pyroptosis after SCI via lncRNAs. Our results showed that TLR4 was activated following SCI and promoted the expression of lncRNA-F630028O10Rik. This lncRNA functioned as a ceRNA for miR-1231-5p/Col1a1 axis and enhanced microglial pyroptosis after SCI by activating the PI3K/AKT pathway. Furthermore, we determined STAT1 was the upstream transcriptional factor of IncRNA-F630028O10Rik and was induced by the damage-responsive TLR4/MyD88 signal. Our findings provide new insights and a novel therapeutic strategy for treating SCI.
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Project description:FOXC1 is a member of Forkhead box family transcription factors. We showed that FOXC1 level was increased in melanoma cells and tissues and correlated with hypomethylation of the FOXC1 gene. Overexpression of FOXC1 promoted proliferation, migration, invasion, colony formation and growth in 3D Matrigel of melanoma cells. FOXC1 increased MST1R and activated the PI3K/AKT pathway. Also, FOXC1 expression was associated with disease progression and poor prognosis of melanoma. We suggest that FOXC1 is a potential prognostic biomarker for treating melanoma and predicting outcome of patients.
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