Project description:We comprehensively analyzed the miRNA expression derived from serum exosomes using microarrays in patients with type 1 AIP (n = 10) in comparison to that in healthy adults (n = 10) and in patient with chronic pancreatitis. The high or low expression of miRNAs in microarray analysis were considered candidate biomarkers or related to the pathogenesis of disease.
Project description: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.
Project description:Autoimmune pancreatitis (AIP) is a disease with unclear immunologic triggers. This study shows that the pancreatic stellate cells(PSCs) are involved in the regulation of the immune response and can cause autoimmunity when the NF-κB signalling in these cells is disrupted. The PSCs were isolated from animals which show autoimmune pancreatitis (NEMO knockout group) or chronic pancreatitis (NEMO wildtype group).
Project description:To identify and assess exosomal miRNA signatures with potential to predict individuals with persistent organ failure (POF) at early phase of acute pancreatitis. We analyzed serum collected from 790 AP patients. In discovery cohort, we profiled exosomal miRNAs in sera sampled from AP patients with or without POF (5 vs. 5) using microarrays and identified a list of miRNAs with increased expression pattern. Of notes, 10 AP samples with/without POF are collected within 24 hours after AP onset and later did/didn’t develop POF. We further constructed a miRNA classifier (Cmi) through logistic regression and identified certain individual miRNAs (OR>2) as candidate predictive markers in the training cohort of 227 AP samples. Predictive performance of these markers were validated in three independent cohorts (255, 226 and 78 AP samples respectively).
Project description:Autoimmune pancreatitis (AIP) is a disease with unclear immunologic triggers. This study shows that the pancreatic stellate cells are involved in the regulation of the immune response and can cause autoimmunity when the NF-κB signalling in these cells is disrupted.
Project description:This project analyzes pancreatic tissue profiles of pancreatic cancer patients, pancreatitis patients, and controls. Since miRNAs are known to be valuable diagnostic markers, we asked whether respective patterns of pancreatic cancer patients can be detected in biopsies. The project aimed at an impoved understanding of complex profiles rather than single markers. Thus, a high-throughput technique was necessary, profiling all known miRNAs integratively. Three markers have been validated by using qPCR. n = 22 normal controls, n = 27 pancreatitis samples, and n = 136 pancreatic cancer samples have been screened for the complete miRNA repertoire. Please note that each miRNA has been measured in seven replicates and the median of the replica has been computed.
Project description:In the current study, we characterized the global miRNA expression profile in mouse pancreatic acinar cells during acute pancreatitis using next-generation RNA-Sequencing. We identified 330 known and 6 novel miRNAs being expressed in mouse pancreatic acinar cells. At basal state, miR-148a-3p, miR-375-3p, miR-217-5p, miR-216a-5p were among the most abundantly expressed whereas miR-24-5p and miR-421-3p were least abundant. Treatment of acinar cells with supra-maximal caerulein or bile acid induced numerous changes in miRNA expression levels. In particular, we observed significant upregulation of miR-21-3p in these experiments, which was further, confirmed using mouse models of acute pancreatitis. In summary, this is the first comprehensive analysis of miRNA expression in healthy mouse pancreatic acinar cells and how this expression signature changes in acute pancreatitis.