Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human pancreas from patients with autoimmune pancreatitis and alcohol-induced chronic pancreatitis

ABSTRACT: Autoimmune pancreatitis (AIP) is a recently identified disease of the pancreas with unknown etiology and antigens. The aim of this study was to determine new target antigens and differentially regulated genes and proteins by means of transcriptomics and proteomics and to validate them in patients with autoimmune pancreatitis. Here we report a distinct downregulation at the RNA and protein level of pancreatic proteases (anionic trypsinogen, cationic trypsinogen, mesotrypsinogen, elastase IIIB) and pancreatic stone protein in autoimmune pancreatitis in comparison to alcohol-induced chronic pancreatitis.

ORGANISM(S): Homo sapiens

SUBMITTER: Ralf Faissner

PROVIDER: E-MEXP-804 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Autoantibodies against the exocrine pancreas in autoimmune pancreatitis: gene and protein expression profiling and immunoassays identify pancreatic enzymes as a major target of the inflammatory process.

Löhr J-Matthias JM Faissner Ralf R Koczan Dirk D Bewerunge Peter P Bassi Claudio C Brors Benedikt B Eils Roland R Frulloni Luca L Funk Anette A Halangk Walter W Jesenofsky Ralf R Kaderali Lars L Kleeff Jörg J Krüger Burkhard B Lerch Markus M MM Lösel Ralf R Magnani Mauro M Neumaier Michael M Nittka Stephanie S Sahin-Tóth Miklós M Sänger Julian J Serafini Sonja S Schnölzer Martina M Thierse Hermann-Josef HJ Wandschneider Silke S Zamboni Giuseppe G Klöppel Günter G

The American journal of gastroenterology 20100420 9

<h4>Objectives</h4>Autoimmune pancreatitis (AIP) is thought to be an immune-mediated inflammatory process, directed against the epithelial components of the pancreas. The objective was to identify novel markers of disease and to unravel the pathogenesis of AIP.<h4>Methods</h4>To explore key targets of the inflammatory process, we analyzed the expression of proteins at the RNA and protein level using genomics and proteomics, immunohistochemistry, western blot, and immunoassay. An animal model of ...[more]

PMID: 20407433

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Project description:Background & Aims: Perturbations in pancreatic ductal bicarbonate secretion often result in chronic pancreatitis. Although the physiological mechanism of ductal secretion is known, its transcriptional control is not well characterized. Here, we investigate the role of the transcription factor Hematopoietically-expressed homeobox protein (Hhex) in pancreatic secretion and pancreatitis. Methods: We derived mice with pancreas-specific, Cre-mediated Hhex gene ablation to determine the requirement of Hhex in the pancreatic duct in early life and in adult stages. Histological and immunostaining analyses were used to detect the presence of pathology. Pancreatic primary ductal cells (PDCs) were isolated to discover differentially expressed transcripts upon acute Hhex ablation. Results: Hhex protein was detected throughout the embryonic and adult ductal trees. Ablation of Hhex in pancreatic progenitors resulted in postnatal ductal ectasia associated with acinar-to-ductal metaplasia, a progressive phenotype that ultimately resulted in chronic pancreatitis. Hhex ablation in adult mice, however, did not cause any detectable pathology. Ductal ectasia did not result from perturbations in primary cilia, but was consistent with the effects of primary ductal hypertension. RNA-seq analysis of Hhex-ablated PDCs indicated the G-protein coupled receptor Natriuretic peptide receptor 3, implicated in paracrine signaling, was upregulated 4.70-fold. Conclusions: Although Hhex is dispensable for adult pancreatic function, ablation of Hhex in pancreatic progenitors results in profound pancreatitis that is consistent with primary ductal hypertension. Our data highlight the critical role of paracrine signaling in maintaining ductal homeostasis, especially in early life, and support ductal hypersecretion as a novel etiology of pediatric chronic pancreatitis. Pancreatic primary ductal cells (PDCs) were isolated from uninduced adult HhexL/L;Sox9CreERT2 (n=2) and littermate control HhexL/L (n=2) mice. PDCs were treated with 500nM 4-hydroxytamoxifen in vitro for 4 days, and then RNA was collected for transcriptome analysis.

Dataset Information

Transcription profiling of human pancreas from patients with autoimmune pancreatitis and alcohol-induced chronic pancreatitis

Publications

Autoantibodies against the exocrine pancreas in autoimmune pancreatitis: gene and protein expression profiling and immunoassays identify pancreatic enzymes as a major target of the inflammatory process.

Similar Datasets

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