Mesenchymal stem cells overexpressing neuropeptide S promote the recovery of rats with spinal cord injury by activating the PI3K/AKT/GSK3β signaling pathway
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1180524 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31181512_1.fastq.gz | Fastqsanger.gz | |||
| SRR31181512_2.fastq.gz | Fastqsanger.gz | |||
| SRR31181513_1.fastq.gz | Fastqsanger.gz | |||
| SRR31181513_2.fastq.gz | Fastqsanger.gz | |||
| SRR31181514_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
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.
| S-EPMC11871753 | biostudies-literature
Project description:Overexpressing EMSCs can significantly improve the therapeutic effect of spinal cord injury in rats, which provides strong support for the feasibility of the use of gene modification of mesenchymal stem cells in clinical applications.
2025-02-19 | GSE280779 | GEO
Project description:Epidemiological investigations have revealed a significant association between alcohol consumption and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Nevertheless, the potential mechanisms are still inadequately revealed. This research aimed to investigate the impact of alcohol on CP/CPPS using an animal model and to elucidate the underlying mechanisms. We first established the widely used animal model for CP/CPPS, experimental autoimmune prostatitis (EAP). During the induction of EAP, mice were fed with alcohol or control diet. The HE staining, ELISA, and behavioral experiments were employed to assess the severity of inflammation in EAP mice and EAP-alcohol mice. Patients with a history of chronic alcohol consumption were also included to evaluate the effects of chronic alcohol consumption on CP/CPPS. Subsequently, proteomic analysis, flow cytometry, immunofluorescence, Western blotting, and immunohistochemistry were utilized to investigate the underlying mechanism involved both in vivo and in vitro. HE staining, ELISA, and behavioral experiments showed that alcohol exacerbated the severity of EAP in mice and patients. Proteomic and KEGG pathway analyses showed that abnormal Th1 differentiation and PI3K/AKT/mTOR pathway were significantly enriched. Subsequent mechanistic research showed that alcohol significantly activated PI3K/AKT/mTOR pathway andincreased the Th1 cell differentiation both in vivo and in vitro. In contrast, PI3K inhibitor LY294002 and shRNA-PI3K plasmid inhibited PI3K/AKT/mTOR pathway activation, reduced Th1 cell differentiation, and alleviated EAP inflammation severity, respectively. Our study is the first to demonstrate that alcohol intake promotes Th1 cell differentiation and exacerbates EAP by activating the PI3K/AKT/mTOR pathway. Additionally, the role of LY294002 in inhibiting PI3K/AKT/mTOR pathway to relieve EAP suggests that it can serveas a promising therapeutic target for CP/CPPS.
2025-01-08 | PXD059384 | Pride
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.
| S-EPMC6929615 | biostudies-literature
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.
| S-EPMC6942383 | biostudies-literature
Project description:Alterations of the tumor suppressor TP53, one of the most common events in cancer, alone are insufficient for tumor development but serve as drivers of transformation. We sought to identify cooperating events through genomic analyses of a novel somatic Trp53R245W mouse model (equivalent to the TP53R248W hot spot mutation in human cancers) that recapitulates metastatic breast cancer development. We identified cooperating lesions similar to those found in human breast cancers. Moreover, we identified activation of the Pi3k/Akt/mTOR pathway in most tumors via mutations in Pten, Erbb2, Kras and/or a recurrent Pip5k1c mutation that stabilizes the Pip5k1c protein to activate Pi3k/Akt/mTOR signaling. Another PIP5K1C family member, PIP5K1A, is co-amplified with PI4KB in 18% of human breast cancer patients and both encode kinases that are responsible for production of the PI3K substrate, phosphatidylinositol 4,5-bisphosphate. Thus, the TP53R248W mutation and PI3K/Akt/mTOR signaling are major cooperative events driving breast cancer development. Additionally, we demonstrated that the upregulation of oxidative phosphorylation by Pi3k/Akt/mTOR signaling is a vulnerability in murine as well as human breast cancer cell lines. These findings advance our understanding of mutant p53-driven breast tumors and expand testable targets for breast cancer treatment.
2022-10-01 | GSE207604 | GEO
Project description:Hepatocellular carcinoma (HCC) remains a global health challenge with high morbidity and mortality. MicroRNAs (miRNAs) play pivotal roles in cancer progression, yet their context-dependent functions in HBV-HCC are unclear. This study demonstrates that miR-424-5p is significantly upregulated in HBV positive Hep3B cells, correlating with poor patient prognosis. Integrated bioinformatic analysis predicted that the target genes of miR-424-5p are significantly enriched in the PI3K/AKT signaling pathway. Functional experiments showed that knockdown of miR-424-5p suppressed cell proliferation, migration, and colony formation. Mechanistically, miR-424-5p knockdown led to the upregulation of PTEN and downregulation of phosphorylated PI3K/AKT, indicating inhibition of this pathway. These findings unveil an oncogenic role of miR-424-5p in HBV-HCC, suggesting its function is driven by viral specific dysregulation of the PI3K/AKT pathway, with PTEN involvement. Our study highlights miR-424-5p as a potential therapeutic target and provides insights into etiology-specific miRNA regulatory networks.
2026-01-21 | GSE316568 | GEO
Project description:Soft tissue sarcoma (STS) is a group of malignancies that can appear in any part of the body. The prognosis of STS patients remains unsatisfactory, mainly due to metastasis and recurrence. Upregulation of KIF20A is associated with poor prognosis of STS patients, but its downstream mechanism is unknown. In the present study, we found that downregulation of KIF20A in the STS cell line HT-1080 inhibits cell proliferation, migration, and invasion and induced cell apoptosis and G2/M arrest in vitro. In addition, downregulation of KIF20A in HT-1080 repressed tumorigenesis of STS in a xenograft mouse model. Pathway analysis showed, that downregulation of KIF20A led to suppression of downstream PI3K-AKT and NF-κB pathways. Specifically, the phosphorylation of AKT at Ser473 was inhibited. Taken together, our results indicate that KIF20A plays an important role in the development of STS by inhibiting cell proliferation, migration, invasion via the PI3K-AKT signaling pathway. Therefore, KIF20A is a potential therapeutic target in STS.
2020-11-23 | GSE140074 | GEO
Project description:Reprogramming of adult somatic cells into induced pluripotent stem cells holds great promise in clinical therapy. Increasing evidences have shown that p53 and its target genes play important roles in somatic cell reprogramming. In this study, we report that PHLDA3, a p53 target gene, functions as a blockage of iPSCs generation by activating the Akt-GSK3β pathway. Furthermore, PHLDA3 is found to be transcriptionally regulated by Oct4. These findings reveal that PHLDA3 acts as a new member of the regulatory network of somatic cell reprogramming.
| S-EPMC5460190 | biostudies-literature
Project description:Hyperactivation of the phosphatydil-inositol-3' phosphate kinase (PI3K)/AKT pathway is observed in most NSCLCs, promoting proliferation, migration, invasion and resistance to therapy. AKT can be activated through several mechanisms that include loss of the negative regulator PTEN, activating mutations of the catalytic subunit of PI3K (PIK3CA) and/or mutations of AKT1 itself. However, number and identity of downstream targets of activated PI3K/AKT pathway are poorly defined. To identify the genes that are targets of constitutive PI3K/AKT signalling in lung cancer cells, we performed a comparative transcriptomic analysis of human lung epithelial cells (BEAS-2B) expressing active mutant AKT1 (AKT1-E17K), active mutant PIK3CA (PIK3CA-E545K) or that are silenced for PTEN. For each sample, 500 ng of total RNA were used to synthesize biotinylated cRNA with Illumina RNA Amplification Kit (Ambion, Austin, TX). Synthesis was carried out according to the manufacturersâ instructions. From each sample, technical triplicates were produced and 750 ng cRNA were hybridized for 18h to Human HT-12_V3_0_R1 Expression BeadChips (Illumina, San Diego, CA). Hybridized chips were washed and stained with streptavidin-conjugated Cy3 (GE Healthcare, Milan, Italy). BeadChips were dried and scanned with an Illumina Bead Array Reader (Illumina).
2016-12-01 | E-MTAB-5286 | biostudies-arrayexpress