Multi-omics analysis of the bladder and its sensitivity to inosine in a rat model of spinal cord injury
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PROVIDER: PRJEB67472 | ENA |
REPOSITORIES: ENA
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Project description:Previously, we demonstrated using a rat model of spinal cord injury (SCI) that bladder wall tissue compliance significantly increased within the first 2 weeks following injury. In order to explore the potential molecular-level mechanisms of this event, the present study quantified molecules pertinent to bladder tissue remodeling and changes in mechanical properties. An initial gene array analysis followed by real-time qPCR revealed that the message levels for tropoelastin and lysyl oxidase were as high as 8-fold in SCI rats compared to normal. Furthermore, both the message and protein levels of TGF-beta1 and IGF-1, known stimulators of elastin synthesis, in SCI rat bladders were significantly higher compared to those of normal rats. Taken together, it can be speculated that functional changes of the bladder associated with SCI induce release of select growth factors, which, in turn, stimulate elastogenesis that lead to alteration of biomechanical properties of the wall tissue.
2008-12-25 | GSE14096 | GEO
Project description:Purpose: In this study, the expression profiles of lncRNAs and mRNAs were explored in the bladder tissue of SCI rats using next-generation sequencing. Methods:Twenty female Wistar rats were randomly divided into SCI 1-3 and normal control (NC) groups. The spinal cord was completely transected at the T9-T10 level to establish the SCI model. Bladder tissues were collected on days 7, 14, and 28 after the operation. The expression profiles of lncRNAs were detected by NGS. Differentially expressed lncRNAs (DELs) were chosen for qRT-PCR verification to validate the RNA sequencing results. Results: Compared with the NC group, the SCI 1-3 groups had 468, 117, and 408 DELs (fold change (FC) > 2), including 282, 38, and 201 up-regulated and 186, 79, and 207 down-regulated lncRNAs, respectively. Likewise, 6654, 2133, and 5706 mRNAs (FC > 2) were differentially expressed between SCI 1-3 and NC rats, of which 4821, 1195, and 3695 were up-regulated, and 1833, 938, and 2011 were down-regulated, respectively. Conclusions: The results revealed the expression profiles and possible roles of lncRNAs in SCI rat NB.
2022-03-02 | GSE197544 | GEO
Project description:Biomarkers of spinal cord injury (SCI) could help determine the severity of the injury and facilitate early critical care decision making. We analyzed global gene expression in peripheral white blood cells during the acute injury phase and identified 197 genes whose expression changed after SCI compared to healthy and trauma controls and in direct relation to SCI severity. Unsupervised co-expression network analysis identified several gene modules that predicted injury severity (AIS grades) with an overall accuracy of 72.7% and included signatures of immune cell subtypes. Specifically, for complete SCIs (AIS ‘A’) ROC analysis showed impressive specificity and sensitivity (AUC: 0.865). Similar precision was also shown for AIS ‘D’ SCIs (AUC: 0.938). Our findings indicate that global transcriptomic changes in peripheral blood cells have diagnostic and potentially prognostic value for SCI severity.
2021-01-22 | GSE151371 | GEO
Project description:In this study, we sough to identify possible new SCI markers by using our CAX-PAGE-LC-MS/MS proteomic platform using SCI biosamples collected from both an SCI animal model (weight-drop) and human clinical studies of SCI patients.
2016-05-10 | PXD003473 | Pride
Project description:Metabolic alteration influences cancer immunity. However, the role and mechanism of metabolic adaption on immune checkpoint blockade (ICB) responses remains ill-defined. Here, metabolomic profiling in mouse tumor models and cancer patients treated with ICB was performed. We found that metabolite inosine was associated with ICB sensitivity in mice and humans, and overcame ICB resistance in several mouse tumor models. Notably, inosine sensitized tumor cells to T cell-mediated cytotoxicity by amplifying tumor-intrinsic immunogenicity. Chemical proteomics further identified that inosine directly bound and inhibited ubiquitin-activating enzyme UBA6. Tumor intrinsic UBA6 loss augmented tumor immunogenicity and substituted the synergistic effect of inosine in combination with ICB. Clinically, tumor UBA6 expression negatively correlated with ICB response in cancer patients. Thus, we reveal an unappreciated function of inosine on tumor-intrinsic immunogenicity and UBA6 as a candidate target for immunotherapy.
2022-08-04 | GSE210225 | GEO
Project description:Cisplatin-based chemotherapy is the first-line treatment for patients with advanced bladder cancer, but the development of cisplatin-resistance limits its anti-tumor effects. Previous studies have shown that cisplatin resistance in bladder cancer may be related to a variety of factors, such as changes in drug transport and metabolism, enhancement of DNA repair mechanisms, changes in cell cycle regulation, inhibition of apoptosis, and epigenetic modification. While, the mechanism of cisplatin resistance is still elusive.In this study, we first found that upregulated ITGB4 is correlated with poor prognosis after chemotherapy in bladder cancer. Next, we demonstrated ITGB4 plays a key role in regulating the sensitivity of bladder cancer to cisplatin therapy. Then, we found that ITGB4 reduced the sensitivity of bladder cancer to cisplatin by inhibiting p53-S15 site phosphorylation and promoting MDM2 binding to p53 to reduce p53 expression. In addition, we demonstrated that ITGB4 regulates the antitumor effects of MDM2 inhibitors combined with cisplatin therapy. Further, we found that ITGB4 was elevated in bladder cancer cisplatin-resistant cells, and the increase in ITGB4 was mediated by STAT3.The combination of STAT3 inhibitors can enhance the antitumor effect of cisplatin in bladder cancer.In summary, we identified ITGB4 as a key molecule affecting cisplatin sensitivity in bladder cancer, and proposed a strategy of combining drugs with STAT3 inhibitors to increase cisplatin sensitivity in bladder cancer.
2024-06-07 | GSE268855 | GEO
Project description:Inosine monophosphate and inosine differentially regulate endotoxemia and bacterial sepsis
| PRJNA762272 | ENA
Project description:The inflammatory response after spinal cord injury (SCI) is an important contributor to secondary damage. Infiltrating macrophages can acquire a spectrum of activation states, however, the microenvironment at the SCI site favors macrophage polarization into a pro-inflammatory phenotype, which is one of the reasons why macrophage transplantation has failed. In this study, we investigated the therapeutic potential of the macrophage secretome for SCI recovery. We investigated the effect of the secretome in vitro using peripheral and CNS-derived neurons and human neural stem cells. Moreover, we perform a pre-clinical trial using a SCI compression mice model and analyzed the recovery of motor, sensory and autonomic functions. Instead of transplanting the cells, we injected the paracrine factors and extracellular vesicles that they secrete, avoiding the loss of the phenotype of the transplanted cells due to local environmental cues. We demonstrated that different macrophage phenotypes have a distinct effect on neuronal growth and survival, namely, the alternative activation with IL-10 and TGF-β1 (M(IL-10+TGF-β1)) promotes significant axonal regeneration. We also observed that systemic injection of soluble factors and extracellular vesicles derived from M(IL-10+TGF-β1) macrophages promotes significant functional recovery after compressive SCI and leads to higher survival of spinal cord neurons. Additionally, the M(IL-10+TGF-β1) secretome supported the recovery of bladder function and decreased microglial activation, astrogliosis and fibrotic scar in the spinal cord. Proteomic analysis of the M(IL-10+TGF-β1)-derived secretome identified clusters of proteins involved in axon extension, dendritic spine maintenance, cell polarity establishment, and regulation of astrocytic activation. Overall, our results demonstrated that macrophages-derived soluble factors and extracellular vesicles might be a promising therapy for SCI with possible clinical applications.
2024-02-14 | PXD048453 | Pride
Project description:The study of male infertility after spinal cord injury (SCI) has enhanced the understanding of seminal plasma (SP) as an important regulator of spermatozoa function. However, the most important factors leading to the diminished sperm motility and viability observed in semen of men with SCI remained unknown. Thus, to explore SP related molecular mechanisms underlying infertility after SCI we used mass spectrometry-based quantitative proteomics to compare SP retrieved from SCI patients to normal controls. As a result, we present an in-depth characterization of the human SP proteome, identifying ~2,800 unique proteins, and describe, in detail, the differential proteome observed in SCI. Our analysis demonstrates that a hyper-activation of the immune system may influence some seminal processes, which probably are not triggered by microbial infection. Moreover, we show evidence of an important prostate gland functional failure, i.e. diminished abundance of metabolic enzymes related to ATP turnover, secreted via prostasomes and identify the main outcome related to this fact and that it is intrinsically linked to the low sperm motility in SCI. Together, our data suggest the molecular pathways hindering fertility in SCI and shed new light on other causes of male infertility.
2016-02-01 | PXD002145 | Pride
Project description:The study models of SCI were established in male Wistar rats with T10 spinal cord contusion. The rat bladders were collected fronm control group (CON group), 1 day after T10 operation group (1_D group), and 7 days after T10 operation group (7_D group), respectively. Then, samples were subjected to proteomic analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and intensive bioinformatic analysis were performed.
2024-05-30 | PXD052697 |