Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

VGF-derived TLQP21 peptide ameliorates tumor progression, pain and depression-like behaviors in an orthotopic mouse model of pancreatic ductal adenocarcinoma

ABSTRACT: In summary, we report that the VGF-derived TLQP21 is a promising target for pharmaceutical interventions in pancreatic ductal adenocarcinoma (PDAC) with dual promise of improving survival outcomes and quality of life in patients with PDAC. Combining bioinformatic analysis of clinical datasets with experimental validations, our study reveals that high VGF expression is correlated with improved survival of PDAC patients. Furthermore, using RNA-Seq analysis and behavioral experiments we found that TLQP21 administration effectively hinders PDAC progression by modulating Tumor-associated macrophages (TAMs), alongside with alleviating depression-like behaviors and allodynia in an orthotopic mouse model of PDAC. Collectively, these findings underscore TLQP21 not only suppresses PDAC progression by modulating TAMs in the tumor microenvironment, but also alleviates pain and depression-like symptoms, highlighting its multifaceted therapeutic potential.

ORGANISM(S): Mus musculus

PROVIDER: GSE277090 | GEO | 2025/06/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

VGF-derived TLQP21 peptide ameliorates tumor progression, pain and depression-like behaviors in an orthotopic mouse model of pancreatic ductal adenocarcinoma

Project description:VGF-derived TLQP21 peptide ameliorates tumor progression, pain and depression-like behaviors in an orthotopic mouse model of pancreatic ductal adenocarcinoma

| PRJNA1160707 | ENA

The NR4A2/VGF pathway fuels inflammation-induced neurodegeneration via promoting neuronal glycolysis

Project description:To find differently expressed genes in VGF overexpressing neuronal cultures.

2024-07-11 | GSE247078 | GEO

SOX9 promotes stress-responsive transcription of VGF nerve growth factor inducible gene in renal tubular epithelial cells

Project description:Acute kidney injury (AKI) is a common clinical condition associated with diverse etiologies and abrupt loss of renal function. In patients with sepsis, rhabdomyolysis, cancer, as well as cardiovascular disorders, the underlying disease or associated therapeutic interventions can cause hypoxic, cytotoxic, and inflammatory insults to renal tubular epithelial cells (RTECs) resulting in the onset of AKI. To uncover stress-responsive disease-modifying genes, here we have carried out renal transcriptome profiling in three distinct murine models of AKI. We find that Vgf nerve growth factor inducible gene upregulation is a common transcriptional stress response in RTECs to ischemia, cisplatin, and rhabdomyolysis-associated renal injury. The Vgf gene encodes a secretory peptide precursor protein that has critical neuro-endocrine functions; however, its role in the kidneys remains unknown. Our functional studies show that RTEC-specific Vgf gene ablation exacerbates ischemia, cisplatin, and rhabdomyolysis-associated AKI in vivo and cisplatin-induced RTEC cell death in vitro. Importantly, addback experiments showed that aggravation of cisplatin-induced renal injury caused by Vgf gene ablation is partly reversed by TLQP-21, a Vgf-derived peptide. Finally, in vitro and in vivo mechanistic studies showed that injury-induced Vgf upregulation in RTECs is driven by the transcriptional regulator Sox9. These findings identify Vgf as an essential stress-responsive gene and reveal a crucial molecular target of the Sox9 regulated transcriptional program that controls epithelial cell fate during AKI.

2020-09-03 | GSE153625 | GEO

Voluntary running triggers VGF-mediated oligodendrogenesis to prolong the lifespan of Snf2h-null ataxic mice

Project description:Exercise enhances cognitive function and slows progressive neurodegenerative disease. While exercise promotes neurogenesis, oligodendrogenesis and adaptive myelination are also significant contributors to brain repair and brain health. Nonetheless, the molecular details underlying these effects remain poorly understood. Conditional ablation of the Snf2h gene (Snf2h cKO) impairs cerebellar development producing mice with poor motor function, progressive ataxia and death between postnatal day 25 to 45. Here we show that voluntary running induced an endogenous brain repair mechanism that resulted in a striking increase in hindbrain myelination and the long-term survival of Snf2h cKO mice. Further experiments identified the VGF growth factor as a major driver underlying this effect. VGF neuropeptides could promote oligodendrogenesis in vitro, while Snf2h cKO mice treated with full-length VGF-encoding adenoviruses obliterated the requirement of exercise for survival. Together, these results suggest that VGF delivery could represent a therapeutic strategy for cerebellar ataxia and other pathologies of the central nervous system.

2016-08-31 | GSE86235 | GEO

Tumor-Derived Exosomal CCT6A Serves as a Matchmaker Introducing Chemokines to Tumor-Associated Macrophages in Pancreatic Ductal Adenocarcinoma

Project description:M2-polarized tumor-associated macrophages (TAMs) are a key factor contributing to the poor prognosis of pancreatic ductal adenocarcinoma (PDAC). While various factors within the tumor microenvironment drive their formation, the role of PDAC-derived exosomes in this process remains unclear. We aim to clarify the regulatory impacts of tumor-derived exosomes to TAMs. Through multi-Omics analysis, we identified CCT6A as a novel tumor-derived exosomal protein, bridging TAMs M2 polarization and PDAC prognosis. Co-culture with exosomes derived from CCT6Ahigh PDAC leads to greater M2 phenotype of TAMs via PI3K-AKT signaling. According to proteomics data, chemokines’ abundance reduces over tenfold once exosomal CCT6A absence, including CXCL1, CXCL3, CXCL20 and CCL5, whose interaction with CCT6A in PDAC cells was confirmed by interactomics data. Morever, we found CCT6A clearance abrogated the antagonism effects of CD47 antibody immunotherapy. The subunit of the T-complex protein Ring Complex (TRiC) CCT6A serves as a matchmaker, during exosomes-mediated chemokines transfer from PDAC to TAMs.

2025-05-26 | PXD056403 | Pride

Quantitative secretomics identifies ligand-receptor pairs in pancreatic cancer that mediate bidirectional crosstalk between cancer stem cells and nociceptors

Project description:Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest and most metastatic cancers in human. PDACs respond poorly to therapies, partly due to cancer stem cells (CSCs) that self-renew, survive chemotherapies, metastasise and replenish the tumour. Factors secreted by tumour cells mediate autocrine/paracrine crosstalk with surrounding cells contributing to the stem cell niche but are still insufficiently characterised. Here we used quantitative SILAC proteomics to identify secreted factors enriched in CSC secretome compared to non-CSCs. Among them were GDF15 and VGF, factors involved in cachexia and pain stimuli. GDF15 and VGF promoted CSC self-renewal and growth through autocrine effects. TGFβ/Activin signalling lowered GDF15 and VGF expression via SMAD2/3-SMAD4-SNON, switching to ATF4-CREB-mediated induction upon cell stress. Co-culture of PDAC-CSCs and hESC-derived neural cells for mimicking cellular crosstalk in PDAC revealed that paracrine signalling via GDF15/VGF promoted nociceptor formation and neurite outgrowth. In turn, Substance P from neurons supported CSC self-renewal, EMT/migration and clonal evolution that was also impacted by SMAD4 genetic status. Lastly, the serum levels of GDF15 and VGF were elevated in PDAC patients suggesting their utility as biomarkers for PDAC detection. Collectively, our data uncovered that cachexia and pain signalling factors mediate the crosstalk between CSCs and nociceptors.

2024-04-06 | PXD046026 | Pride

CHIP controls the expression of the neuropeptide precursor protein VGF

Project description:CHIP is a neuroprotective E3-ubiquitin ligase that supports longevity and healthy ageing. Loss of CHIP function has a major impact on life expectancy in animal models, whilst in humans’ mutations that compromise the E3-ligase activity of CHIP are causative for forms of Spinocerebellar Ataxia (SCA) that are accompanied by cognitive decline and/or dementia. The pathways regulated by CHIP to maintain neuronal health remain to be discovered. Gene-edited neuroblastoma cells were produced and used as a model to study the effects of CHIP loss on the steady state proteome in the absence of proteotoxic stress. Label free quantitative proteomic analysis (SWATH-MS) highlighted VGF, a member of the neuropeptide precursor family of proteins, as being a dominant protein responding to loss of CHIP function. By studying the dependence of VGF expression on CHIP using SILAC and RNA-Seq we have defined a role for the ligase in regulated neuropeptide expression.

2021-07-29 | PXD016299 | Pride

VGF-derived peptide attenuates development of type 2 diabetes via enhancement of islet beta cell survival and function survival and function

Project description:Deterioration of functional islet β-cell mass is the final step in progression to Type 2 diabetes. We previously reported that overexpression of Nkx6.1 in rat islets has the dual effects of enhancing glucose-stimulated insulin secretion (GSIS) and increasing β-cell replication. Here we show that Nkx6.1 strongly upregulates the prohormone VGF in rat islets and that VGF is both necessary and sufficient for Nkx6.1-mediated enhancement of GSIS. Moreover, the VGF-derived peptide TLQP-21 potentiates GSIS in rat and human islets and improves glucose tolerance in vivo. Chronic injection of TLQP-21 in pre-diabetic ZDF rats preserves islet mass and slows diabetes onset. TLQP-21 prevents islet cell apoptosis by a pathway similar to that used by GLP-1, but independent of the GLP-1, GIP, or VIP receptors. Unlike GLP-1, TLQP-21 does not inhibit gastric emptying or increase heart rate. We conclude that a TLQP-21 is a novel agent for enhancing islet β-cell survival and function. We utilized a “sample x reference” experimental design strategy in which RNA extracted from rat pancreatic islets was hybridized to the microarray slide in the presence of labeled rat reference RNA (RRR, Stratagene, LaJolla, CA). Cultures were treated with adenoviruses expressing either the hamster form of Nkx6.1, the mouse form of Pdx1, or the beta-galactosidase enzyme. 3-5 biological replicates each representing independent islet isolations were used for microarray analysis. Briefly, five hundred nanograms of total RNA were used for gene expression profiling following reverse transcription and T-7 polymerase-mediated amplification/labeling with Cyanine-5. Labeled subject cRNA was co-hybridized to Operon rat 27K oligonucleotide arrays with equimolar amounts of Cyanine-3 labeled RRR. Slides were hybridized, washed, and scanned on a Gene Pix 5000 microarray scanner.

2012-05-09 | E-GEOD-37852 | biostudies-arrayexpress

Tumor-Derived Exosomal CCT6A Serves as a Matchmaker Introducing Chemokines to Tumor-Associated Macrophages in Pancreatic Ductal Adenocarcinoma [mouse RNA-seq]

2025-03-28 | GSE278339 | GEO

Tumor-Derived Exosomal CCT6A Serves as a Matchmaker Introducing Chemokines to Tumor-Associated Macrophages in Pancreatic Ductal Adenocarcinoma [human RNA-seq]

2025-04-06 | GSE278909 | GEO