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Disease associated fibroblasts from various pancreatic disorders exhibit subtype specific genetic profile [miRNA]

ABSTRACT: Currently it is unknown whether activation of recruited or resident pancreatic fibroblasts, including pancreatic stellate cells activation, create a common “fibroblast-activated phenotype” indistinguishable from their associated-diseased microenvironment . Using a combination of microRNA and mRNA profiling of fibroblasts isolated from pancreatic ductal adenocarcinoma (PDAC), chronic pancreatitis (CP), periampullary cancer (PAT) and areas of histologically normal pancreas, followed by comprehensive validation, we show that activated fibroblasts derived from different pancreatic disease types are considerably distinct.

ORGANISM(S): synthetic construct Homo sapiens

PROVIDER: GSE123377 | GEO | 2020/07/14

REPOSITORIES: GEO

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Disease associated fibroblasts from various pancreatic disorders exhibit subtype specific genetic profile [RNA]

Project description:Currently it is unknown whether activation of recruited or resident pancreatic fibroblasts, including pancreatic stellate cells activation, create a common “fibroblast-activated phenotype” indistinguishable from their associated-diseased microenvironment . Using a combination of microRNA and mRNA profiling of fibroblasts isolated from pancreatic ductal adenocarcinoma (PDAC), chronic pancreatitis (CP), periampullary cancer (PAT) and areas of histologically normal pancreas, followed by comprehensive validation, we show that activated fibroblasts derived from different pancreatic disease types are considerably distinct.

2020-07-14 | GSE123375 | GEO

NADPH Oxidase 1 in Chronic Pancreatitis-Activated Pancreatic Stellate Cells Facilitates the Progression of Pancreatic Cancer

Project description:Aims: Patients suffering from chronic pancreatitis (CP) have a higher risk of pancreatic ductal adenocarcinoma (PDAC). NADPH oxidase 1 (Nox1) in activated pancreatic stellate cells from a CP mouse model (CP-activated PaSCs) forms fibrotic tissue and up-regulates matrix metalloproteinase (MMP) 9. Yet, the role and mechanism of Nox1 in CP-activated PaSCs in the progression of PDAC is unknown. 1) We tested the ability of Nox1 in CP-activated PaSCs to facilitate the growth and invasion of pancreatic cancer cells. 2) We identified proteins in the secretome of CP-activated PaSCs whose production was Nox1-dependent. Results: In vitro, Nox1 in CP-activated PaSCs facilitated the migration/invasion of MIA PaCa-2 and HPAC cells. Nox1 evoked a both pro-invasive and cancer-promoting phenotype in PaSCs via a paracrine activation of both p38 MAPK and STAT3 pathways in neoplastic cells. In vivo, Nox1 in CP-activated PaSCs facilitated tumor growth, metastasis formation, and stromal expansion. Using mass spectrometry, we identified proteins protecting from cellular stresses in the secretome of CP-activated PaSCs whose production was Nox1-dependent. Innovation: Inhibiting the stromal Nox1 signaling at early stages can reduce the reorganization of histological barriers, and the protection of neoplastic cells from cellular stresses, ameliorating the progression of PDAC. Conclusions: Nox1 in CP-activated PaSCs induced both Twist1 and MMP-9 expression, causing changes in the extracellular matrix composition. In addition, Nox1 oxidized peroxiredoxins 1 and 4 through thioredoxin reductase 1, causing p38 MAPK and STAT3 phosphorylation in neoplastic cells when they were secreted from CP-activated PaSCs. Both mechanisms facilitated the progression of PDAC.

2023-03-10 | PXD034177 | Pride

Single-cell transcriptomic analysis of mouse pancreas: characteristic features of pancreatic ductal cells in chronic pancreatitis

Project description:Chronic pancreatitis (CP) is a pathogenically complex fibro-inflammatory disorder of the pancreas. Our understanding of CP pathogenesis is partly limited by the incomplete characterization of pancreatic cell types. Here, we performed single-cell RNA sequencing on 3,386 cells from the pancreas of one control mouse and mice with caerulein-induced CP. These data provides a preliminary description of the single-cell transcriptome profiles of mouse pancreata and accurately demonstrates the characteristics of pancreatic ductal cells in CP.

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Global microRNA expression profiling of microdissected tissues from diseased and non-diseased pancreatic tissues

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Microarray gene-expression data to validate a 17-gene biomarker obtained from excessive meta-analysis to test its PDAC specificity in the presence of pancreatitis tissues.

Project description:Clinical signs and radiographic findings of PDAC and pancreatitis are often indistinguishable, highlighting the need of a PDAC biomarker to be insensitive to pancreatitis. Therefore we validated a biomarker signature of 17-genes in this gene expression data containing PDAC, non-tumor pancreatic and pancreatitis of fresh-frozen and formalin-fixed paraffin-embedded tissues.

2018-05-11 | GSE101462 | GEO

Potential regulatory proteins in pancreatitis were screened by proteomics using pancreatic tissues of PRSS1 AP mice

Project description:Humanized PRSS1 transgenic mice were constructed and treated with caerulein to mimic the development of human AP and CP. Potential regulatory proteins in pancreatitis were screened by proteomics using pancreatic tissues of PRSS1 AP mice.

2021-09-09 | PXD016651 | Pride

Potential ATF6 regulatory proteins were screened by proteomics using pancreatic tissues of PRSS1 transgenic mice treated with caerulein

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Global microRNA expression profiling of microdissected tissues from diseased and non-diseased pancreatic tissues

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Chronic pancreatitis vs pancreatic cancer LC-MS

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