SOX11 Downregulation and IL-7/IL22RA2 Upregulation Might be a Potential Mechanism of Exosome in Promoting Schwann Cell Proliferation
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE315249 | GEO | 2026/01/04
REPOSITORIES: GEO
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Project description:Background: Adipose-derived stem cells (ADSCs) can differentiate into Schwann cells (SCs) at the site of nerve injury, where Schwann cell-derived exosomes (SC-Exos) are suspected to exert an induction effect. Our study aimed to induce the differentiation of ADSCs in vitro using SC-Exos and to investigate the mechanisms involved through miRNA sequencing. Methods: Subcutaneous fat was used to extract ADSCs. Exosomes were extracted from Schwann cell lines (RSC96) using ultracentrifugation. After 8 days of induction of ADSCs by SC-Exos, phenotypic characteristics were observed by examining the expression of SC markers (S100, NGFR, MPZ, GFAP) through RT-qPCR, Western blot and immunofluorescence. Additionally, miRNA sequencing was performed on induced ADSCs, followed by bioinformatic analysis and validation of the results. Results: SC-Exos were taken up by human ADSCs. The RNA and protein expression levels of S100, NGFR, MPZ and GFAP were found to be significantly higher in the SC-Exo induction group than in the uninduced group, despite no significant difference to the Dezawa’s method group, which was also consistent with the immunofluorescence results. According to the sequencing results, there were a total of 72 differentially expressed miRNAs. Bioinformatics analysis indicated that 3506 Gene Ontology terms and 98 Kyoto Encyclopedia of Genes and Genomes pathways were significantly enriched. Ten miRNAs, 6 target mRNAs and elevated expression of the PIK3CD/Akt pathway were validated by RT-qPCR or Western blot, which is consistent with the sequencing results. Conclusions: Our data suggest that SC-Exos are able to induce the differentiation of ADSCs into SCs in vitro. It is speculated that the differentially expressed miRNAs play a significant role in the differentiation process.
2022-02-13 | GSE183623 | GEO
Project description:Background: Following spinal cord injury (SCI), the inflammatory storm initiated by microglia/macrophages poses a significant impediment to the recovery process. Exosomes play a crucial role in the transport of miRNAs, facilitating essential cellular communication through the transfer of genetic material. However, the miRNAs from iPSC-NSCs-Exos and their potential mechanisms leading to repair after SCI remain unclear. This study aims to explore the role of iPSC-NSCs-Exos in microglia/macrophage pyroptosis and reveal their potential mechanisms. Methods: iPSC-NSCs-Exos were characterized and identified using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. A mouse SCI model and a series of in vivo and in vitro experiments were conducted to investigate the therapeutic effects of iPSC-NSCs-Exos. Subsequently, miRNA microarray analysis and rescue experiments were performed to confirm the role of miRNAs in iPSC-NSCs-Exos in SCI. Mechanistic studies were carried out using Western blot, luciferase activity assays, and RNA-ChIP. Results: Our findings revealed that iPSC-NSCs-derived exosomes inhibited microglia/macrophage pyroptosis at 7 days post-SCI, maintaining myelin integrity and promoting axonal growth, ultimately improving mice motor function. The miRNA microarray showed let-7b-5p to be highly enriched in iPSC-NSCs-Exos, and LRIG3 was identified as the target gene of let-7b-5p. Through a series of rescue experiments, we uncovered the connection between iPSC-NSCs and microglia/macrophages, revealing a novel target for treating SCI. Conclusion: In conclusion, we discovered that iPSC-NSCs-derived exosomes can package and deliver let-7b-5p, regulating the expression of LRIG3 to ameliorate microglia/macrophage pyroptosis and enhance motor function in mice after SCI. This highlights the potential of combined therapy with iPSC-NSCs-Exos and let-7b-5p in promoting functional recovery and limiting inflammation following SCI.
2024-07-17 | GSE267739 | GEO
Project description:The use of dermal papilla cells for hair follicle (HF) regeneration is long accepted much attention. However, cultured dermal papilla cells tend to lose the hair-inducible capability during passaging, which restricts its application. Increasing evidences indicate that dermal papilla cells exert their regulatory function of HF growth mainly through their unique paracrine properties, opening up a way to exosome therapies.This study aimed to explore the effects of exosomes from high and low-passaged human scalp follicle dermal papilla cells (DP-Exos) on hair follicle stem cells (HFSCs) activation and hair growth, and to investigate the underline mechanism. DP-Exos were isolated by ultracentrifugation and cultured with human scalp follicles and HFSCs. The hair elongation and cell proliferation was assessed. Quantitative real-time PCR (qRT-PCR) and Western-blot were performed to detect the expression levels of a class of miRNAs and proteins which have positive roles in regulating hair growth and HFSCs proliferation. High throughput miRNA sequencing of miRNAs in high (P8) and low-passaged (P3) DP-Exos was performed, and the utmost miRNA and its target gene was identified via bioinformatics analysis.
2021-01-13 | GSE136241 | GEO
Project description:Rationale：Poor peri-implant osseointegration of dental implants in patients with type II diabetes has become a major clinical challenge in recent years. MSC (Mesenchymal stem cell)-derived exosomes may play an important role in peri-implant osseointegration, but the mechanism remains unclear. Enhancing the therapeutic effect of MSC-derived exosomes and exploring the potential mechanism can help provide a new therapeutic strategy to improve the clinical outcome of dental implant restorations in patients with type II diabetes. Methods：The exosomes derived from hypoxia (Hypo-exos) or normoxia (Nor-exos) preconditioned bone marrow mesenchymal stem cells (BMSCs) were co-cultured with BMSCs and human umbilical vein endothelial cells (HUVECs). The effect of exosomes on BMSCs cell proliferation was detected by CCK-8 assay and EdU assay, and the effect on angiogenesis ability of HUVECs was detected by wound healing assay, transwell migration assay, tube formation assay, enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. A diabetic rat dental implant model was also established and the effect of exosomes on implant osseointegration was evaluated through micro-CT scanning and histological analysis. The differentially expressed miRNAs between Hypo-exos and Nor-exos were identified by high-throughput miRNA sequencing. Subsequently, the target genes and their roles in regulating angiogenesis were predicted and analyzed by bioinformatics analysis and dual luciferase reporter assay. Results：In vitro experiments indicated that hypoxia preconditioning could elevate exosome production and promote cell proliferation of BMSCs and angiogenesis of HUVECs. Moreover, Hypo-exos promoted peri-implant osteogenesis in rats with diabetes. Further investigation revealed the vital involvement of the miR-106b-5p/HIF-1α axis in promoting peri-implant osseointegration. Conclusion: Exosomes derived from hypoxia-preconditioned BMSCs could improve the peri-implant osseointegration in rats with diabetes by promoting cell proliferation and angiogenesis, and the miR-106b-5p/ HIF-1α axis could be the underlying mechanism.
2024-09-04 | GSE275863 | GEO
Project description:Peripheral nerve injury (PNI) is a major clinical and public health challenge that frequently results in significant functional impairment and permanent disability. However, most peripheral nerve injury-repairing strategies offer unsatisfactory clinical outcomes. Exosomes act as key mediators of the paracrine effects of induced pluripotent stem cells (iPSC-Exos), showing significant therapeutic promise for various conditions. Still, their efficacy and safety remain a major concern. Therefore, this study investigates the regeneration potential and safety of iPSC -Exos in a rat sciatic nerve crush injury model. Sendai virus vectors were used to reprogram peripheral blood mononuclear cells (PBMCs) from healthy donors into iPSCs. The cells were subsequently examined for pluripotency and karyotype integrity and validated using in vivo teratoma assays. iPSC-Exos were isolated and identified using transmission electron microscopy, nanoparticle tracking analysis, western blotting, and cell viability. In vivo, iPSC-Exos was injected directly at the injury site. Gait analysis, grip strength evaluation, and mechanical pain were measured preoperation and at 7, 14, 21, and 28 days postoperation. Animals' weight, hematology indexes, key organ weight, and histological changes were evaluated. Morphological analysis of regenerated nerve and muscle was examined. The immunofluorescence staining evaluated axon regeneration, remyelination, Schwann cells (SCs), and angiogenesis in the sciatic nerve at 2 and 4 weeks post-operation. Real-time PCR was used to assess gene-level expression associated with nerve regeneration. RNA sequencing (RNA-seq) was conducted to identify differentially expressed genes (DEGs) and pathways in experimental groups. PBMC-derived iPSCs exhibited Embryonic Stem cells-like morphology, showed pluripotency markers, preserved a normal karyotype, and induced teratomas, including tissues from all germ layers. After isolating and validating exosomes, PKH26-labeled exosomes were efficiently absorbed by SCs and enhanced SCs proliferation in a concentration-dependent manner in vitro. Safety evaluations revealed no adverse effect on the overall body weight, organ weight, hematological parameters, or histological changes of key organs. Exosome injection significantly improved gait analysis, grip strength, pain response, gastrocnemius muscle atrophy, axonal regrowth, myelin formation, and neovascularization. Furthermore, quantitative Real-time PCR (qPCR) results indicated an increase in regeneration-associated transcripts. RNA-seq analysis identified the upregulation of genes involved in nerve repair, with enrichment of pathways such as PI3K-AKT signaling, focal adhesion, and calcium signaling.Exosomes derived from iPSCs show a safe, effective, and non-cell-based therapeutic approach for PNIs. Their ability to promote axonal regrowth, myelin formation, and angiogenesis demonstrates their potential for clinical applications in regenerative medicine.
2025-04-16 | GSE286150 | GEO
Project description:Osteoarthritis (OA) is a progressive degenerative joint disorder characterized by chondrocyte dysfunction and extracellular matrix degradation. While stem cell therapies have been constrained by immunological rejection risks, their derived extracellular vesicles (Exos) emerge as a promising alternative therapeutic approach. Antler, a remarkable regenerative organ with extraordinary regenerative capacity and chondrogenic potential, offers a unique biological resource. Antler Stem Cells (ASCs) provide an innovative extracellular vesicle source (ASC-Exos) that presents a compelling therapeutic strategy for addressing OA's complex pathogenesis. To investigate the therapeutic effects and mechanism of ASC-Exos in OA treatment. ASCs characteristics were confirmed through immunofluorescence and tri-lineage differentiation, while exosomes were validated using transmission electron microscopy, nanoparticle tracking analysis, and Western blot. A rat OA model was established to evaluate therapeutic effects of ASC-Exos via different administration routes. Small RNA sequencing identified key extracellular vesicle components, while dual-luciferase reporter assays confirmed regulatory interactions between miR-140 and metalloproteinase-13(MMP13). Stable miR-140 overexpressing ASCs were generated through lentiviral transduction. An IL-1β-stimulated chondrocyte OA model was employed to assess the impact of miR-140-engineered ASC-Exos (miR-140-Exos) on cellular proliferation, migration, and apoptosis. The therapeutic potential was further evaluated in in vivo animal models. We successfully isolated and characterized ASCs and ASC-Exos. Intra-articular injection of ASC-Exos demonstrated superior cartilage repair efficacy. The critical extracellular vesicle component miR-140 was identified. In vitro studies revealed that miR-140-Exos significantly enhanced chondrocyte proliferation and migration while reducing cellular apoptosis. Dual-luciferase assays confirmed miR-140 directly targets MMP13, with MMP13 overexpression partially reversing miR-140-mediated cellular effects. In vivo investigations demonstrated that miR-140-modified ASC-Exos effectively inhibited COL II degradation and suppressed NLRP3 elevation, thereby providing anti-inflammatory benefits and promoting cartilage regeneration. miR-140-Exos represent an innovative therapeutic approach for osteoarthritis, effectively promoting cartilage regeneration and alleviating inflammation through MMP13 inhibition, presenting a novel therapeutic strategy for OA treatment.
2025-09-03 | GSE306940 | GEO
Project description:<p>Cycloleucine (CL) is a methyl donor inhibitor. Our previous findings showed that CL could affect meiotic maturation and developmental potency of porcine oocytes by reducing nucleic acid N6-methyladenosine (m6A) epigenetic modification level. However, the effects of CL on porcine male reproduction are unclear. Here，we showed that CL treatment of porcine Sertoli cells (SCs) could reduce viability in a dose-dependent manner. CL treatment (40mM, 36h) of porcine SCs also inhibited proliferation, promoted late apoptosis, increased level of intracellular reactive oxygen species (ROS), reduced mitochondrial function, suppressed levels of nucleic acid N6-methyladenosine (m6A), H3K4me3, H3K27ac and H4K16ac, and increased H3K9me2 level. ELISA assays showed that CL (40mM, 36h) decreased lactate production, but unaltered levels of anti-Müllerian hormone and estradiol. RNA-seq and metabolomics identified 1212 differentially expressed genes (DEGs) (536 up- and 676 down-) and 67 significantly different metabolites (SDMs) (45 up- and 22 down-) to be altered by CL (40mM, 36h) treatment of porcine SCs. These DEGs and SDMs were involved in multiple pathways, including PI3K-Akt, cell cycle, Glycolysis/Gluconeogenesis, FoxO, aminoacyl-tRNA biosynthesis etc. Some of DEGs were validated at mRNA and protein levels. Combined analysis of transcriptome and metabolome identified the high correlations between some DEGs and SDMs. These findings indicate that CL could affect functions of porcine SCs by modifying epigenetic modifications to alter gene expression and metabolism.</p>
2025-09-13 | MTBLS12990 | MetaboLights
Project description:Purpose: To compare the transcriptional changes of genes in dental pulp tissues with different degrees of inflammatory severity and investigate the role of RAD54B in inflamed human dental pulp cells (hDPCs) Methods: Normal, carious, and pulpitis human dental pulp tissues were collected. Total RNA extracted were subjected to RNA-sequencing and gene expression profiles were further studied by Gene Ontology (GO) and KEGG pathway analysis. DEGs (differentially expressed genes) in homologous recombination repair (HRR) were validated with qRT-PCR. The expression of RAD54B and TNF-α in human dental pulp tissues was detected by immunohistochemistry. HDPCs were cultured and RAD54B level in hDPCs was detected after LPS stimulation using western blot. CCK-8 was applied to investigate the cell proliferation of hDPCs transfected with negative control (Nc) small interfering RNA (siRNA), RAD54B siRNA, P53 siRNA or both siRNAs with or without LPS stimulation. Flow cytometry was applied to detect the cell cycle distribution, and western blot and immunofluorescence were utilized to analyze the expression of RAD54B, P53 and P21 under the above treatments. One-way and two-way ANOVA followed by LSD posttest were used for statistical analysis. Results: RNA-sequencing results identified DEGs among three groups. KEGG pathway analysis revealed enrichment of DEGs in Replication and Repair pathway. HRR and non-homologous end joining (NHEJ) components were further verified and qRT-PCR results were basically consistent with the sequencing data. RAD54B, a HRR accessory factor highly expressed in carious and pulpitis tissues compared to normal pulp, was chosen as our gene of interest. High RAD54B expression was confirmed in inflamed human dental pulp tissues and LPS-stimulated hDPCs. Upon RAD54B knockdown, P53 and P21 expressions in hDPCs were upregulated whereas the cell proliferation was significantly downregulated, accompanied with increased G2/M phase arrest. After inhibiting P53 expression in RAD54B-knockdown hDPCs, P21 expression and cell proliferation were reversed. Conclusions: Gene expression profiles of normal, carious and pulpitis human dental pulp tissues were revealed. HRR components was elucidated to function in dental pulp inflammation. Among HRR DEGs, RAD54B could regulate the cell proliferation of inflamed hDPCs via P53/P21 signaling. This research not only deepens our understanding of dental pulp inflammation but also provides a new insight to clarify the underlying mechanisms.
2023-09-02 | GSE198359 | GEO
Project description:In this study,RAC1 expression was silenced by RNA interference in colon cancer cell lines, and investigate the correlation between RAC1 expression and colon cancer proliferation,and differential expressed genes were analized by gene assay and qPCR technologe.The proliferation and colony formation ability of colon cancer cells were significantly reduced after RAC1 knockdown. More 1200 known genes were found to be involved in the RAC1 functions related tumorigenesis by genechip analysis, these genes related to cell proliferation/apoptosis and cell cycle process. qRT-PCR results showed an expression pattern consistent with that of the genechip analysis. Lentivirus-mediated RNA interference was used to knockdown RAC1 expression in colon cancer cell lines. And cell proliferation assays . GeneChip analysis were carried out for mRNA expression profiling, followed, the expressed levels of mRNA and protein were measured by Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot, respectively.
2016-02-20 | E-GEOD-78093 | biostudies-arrayexpress
Project description:In this study,YWHAE expression was silenced by RNA interference in colon cancer cell lines, and investigate the correlation between YWHAE expression and colon cancer proliferation,and differential expressed genes were analized by gene assay and qPCR technologe.The proliferation and colony formation ability of colon cancer cells were significantly reduced after YWHAE knockdown. More 1200 known genes were found to be involved in the YWHAE functions related tumorigenesis by genechip analysis, these genes related to cell proliferation/apoptosis and cell cycle process. qRT-PCR results showed an expression pattern consistent with that of the genechip analysis. Lentivirus-mediated RNA interference was used to knockdown YWHAE expression in colon cancer cell lines. And cell proliferation assays . GeneChip analysis were carried out for mRNA expression profiling, followed, the expressed levels of mRNA and protein were measured by Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot , respectively.
2016-02-20 | E-GEOD-78094 | biostudies-arrayexpress