Comprehensive Analysis of Serum microRNAs in Autoimmune Pancreatitis

Hamada, Shin; Masamune, Atsushi; Kanno, Atsushi; Shimosegawa, Tooru

doi:10.1159/000381283

Cited by 18 publications

(16 citation statements)

References 41 publications

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“…Dysregulated expression of miR-150-5p in immune cells could result in autoimmune diseases [38]. MiR-150-5p was reported to be over-expressed in autoimmune pancreatitis compared to chronic pancreatitis, pancreatic cancer and healthy controls [39]. Based on our observations miR-150-5p is down-regulated in pSS, on the contrary, in SLE patients, miR-150-5p expression levels were not decreased but elevated, albeit not significantly.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA expression profiles identify disease-specific alterations in systemic lupus erythematosus and primary Sjögren's syndrome

et al. 2017

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The discovery of microRNAs (miRNAs) and their critical role in genetic control opened new avenues in understanding of various biological processes including immune cell lineage commitment, differentiation, proliferation and apoptosis. However, a given miRNA may have hundreds of different mRNA targets and a target might be regulated by multiple miRNAs, thus the characterisation of dysregulated miRNA expression profiles could give a better insight into the development of immunological disturbances in autoimmune diseases. The aim of our study was to examine the changes in miRNA expression profiles in patients with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). Eight SLE patients, 8 pSS patients and 7 healthy subjects were enrolled in the investigation. MiRNAs were isolated from peripheral blood mononuclear cells, and expression patterns were determined with Illumina next-generation sequencing technology. Since the immunopathogenesis of pSS and SLE encompasses pronounced B cell hyperactivity along with specific autoantibody production, we paid a special attention on the association between miRNA expression levels and altered peripheral B cell distribution. In SLE patients 135, while in pSS patients 26 miRNAs showed altered expression. Interestingly, the 25 miRNAs including miR-146a, miR-16 and miR-21, which were over-expressed in pSS patients, were found to be elevated in SLE group, as well. On the contrary, we observed the down-regulation of miR-150-5p, which is a novel and unique finding in pSS. Levels of several miRNAs over-expressed in SLE, were not changed in pSS, such as miR-148a-3p, miR-152, miR-155, miR-223, miR-224, miR-326 and miR-342. Expression levels of miR-223-5p, miR-150-5p, miR-155-5p and miR-342-3p, which miRNAs are potentially linked to B cell functions, showed associations with the B cell proportions within peripheral blood mononuclear cells. The observed differences in miRNA expression profiles and the better understanding of immune regulatory mechanisms of miRNAs may help to elucidate the pathogenesis of SLE and pSS.

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Section: Discussionmentioning

confidence: 99%

MicroRNA expression profiles identify disease-specific alterations in systemic lupus erythematosus and primary Sjögren's syndrome

et al. 2017

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“…It is reasonable to assume that altered immune reactions in AIP and long-standing malnutrition in CP modify the dysbiosis. In addition, it would be of interest to see whether gut microbiota profiles are useful to diagnose early CP, distinguish AIP from CP, and predict disease relapses in AIP (Hamada et al 2015;Masamune et al 2017a, b). We here report comprehensive analysis of gut microbiota in patients with AIP and those with CP.…”

Section: Introductionmentioning

confidence: 99%

Differences in Gut Microbiota Profiles between Autoimmune Pancreatitis and Chronic Pancreatitis

Hamada

Masamune

Nabeshima

et al. 2018

Tohoku J. Exp. Med.

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Host-derived factors alter gut microenvironment, and changes in gut microbiota also affect biological functions of host. Alterations of gut microbiota have been reported in a wide variety of diseases, but the whole picture of alterations in pancreatic diseases remains to be clarified. In particular, the gut microbiota may be affected by malnutrition or impaired exocrine pancreas function that is associated with pancreatic diseases. We here conducted comprehensive analysis of gut microbiota in patients with type 1 autoimmune pancreatitis (AIP), a pancreatic manifestation of the systemic IgG4-related disease, and chronic pancreatitis (CP). The two diseases were selected, because altered immune reactions in AIP and/ or long-standing malnutrition in CP may influence the gut microbiota. Fecal samples were obtained from 12 patients with AIP before the steroid therapy and 8 patients with CP. Metagenome DNA was extracted, and microbiota was analyzed by next generation sequencing. Gut microbiota profiles were different between patients with AIP and those with CP; namely, the proportions of Bacteroides, Streptococcus and Clostridium species were higher in patients with CP. The reasons for the increased proportion of these bacterial species remain unknown, but may reflect malabsorption and/or decreased pancreatic enzymes, both of which are associated with CP. Incidentally, the identified Streptococcus species are oral cavity inhabitants and also known as pathogens for endocarditis. Despite the small sample size, this study has shown the differences in gut microbiota profiles between AIP and CP. Comprehensive analysis of the gut microbiota may be useful for the differential diagnosis of pancreatic diseases.

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“…In 2008, Jeyasee et al first discovered the presence of miRNAs in circulating blood, and since then miRNAs have been demonstrated to be stably present in various extracellular body fluids, including plasma, serum, urine, tears, and lymph (11,21,22). Extracellular miRNAs could integrate into recipient cells and interfere with target mRNAs to regulate the function of recipient cells (23)(24)(25). The miRNAs in circulating plasma or serum are packaged into microvesicles and exosomes.…”

Section: Discussionmentioning

confidence: 99%

Screening and validation of differentially expressed extracellular miRNAs in acute pancreatitis

Meng

Wang

Xue

et al. 2017

Molecular Medicine Reports

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The present study aimed to screen for differentially expressed extracellular microRNAs (miRNAs) during the development of acute pancreatitis (AP) and validate the miRNA expression in the plasma of patients with AP. The culture medium of taurolithocholic acid‑3 sulfate‑treated rat pancreatic acinar AR42J cells was collected to extract total RNA for miRNA microarray analysis. Compared with the miRNA test results of the AP rats in the GEO databases, the differentially expressed extracellular miRNAs were screened. The TargetScan, miRanda, and PicTar programs were used for target gene prediction of the identified miRNAs, and gene ontology‑biological processes (GO‑BP) functional annotation was performed. Finally, the results from the combined microarray analyses (in vitro cell line and in vivo rat samples) were validated using plasma samples from patients with mild and moderately severe AP by reverse transcription‑polymerase chain reaction. The results demonstrated that extracellular miR‑24 was differentially expressed by microarray and bioinformatics analysis in both the cell line and the animal model of AP. Bioinformatics prediction analysis revealed that downstream target genes of miR‑24 included Vav2, Syk, Lhcgr, Slc9a3r1, Cacnb1, Cacna1b, Bcl10, and Fgd3. Functional enrichment analysis revealed that the main GO‑BP predicted functional presentations were positive regulation of calcium‑mediated signaling, activation of c‑Jun N‑terminal kinase activity, calcium ion transport, regulation of Rho protein signal transduction, negative regulation of the protein kinase B signaling cascade, and the T cell receptor signaling pathway. Validation analysis for the plasma miR‑24 expression in humans revealed a significant upregulation of miR‑24 in the plasma samples of AP patients compared with the healthy controls, while no significant difference was observed in the miR‑24 expression between the mild and the moderately severe AP groups. The present study confirmed the high expression of miR‑24 in peripheral blood during AP, suggesting that miR‑24 might have an intercellular communication role contributing to the AP‑associated distant organ injury.

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Comprehensive Analysis of Serum microRNAs in Autoimmune Pancreatitis

Cited by 18 publications

References 41 publications

MicroRNA expression profiles identify disease-specific alterations in systemic lupus erythematosus and primary Sjögren's syndrome

MicroRNA expression profiles identify disease-specific alterations in systemic lupus erythematosus and primary Sjögren's syndrome

Differences in Gut Microbiota Profiles between Autoimmune Pancreatitis and Chronic Pancreatitis

Screening and validation of differentially expressed extracellular miRNAs in acute pancreatitis

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