Dataset Information

Differential Hrd1 Expression and B-Cell Accumulation in Eosinophilic and Non-eosinophilic Chronic Rhinosinusitis With Nasal Polyps.

ABSTRACT:

Purpose

Hrd1 has recently emerged as a critical regulator of B-cells in autoimmune diseases. However, its role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) remains largely unexplored. This study aimed to examine Hrd1 expression and B-cell accumulation and their possible roles in CRSwNP.

Methods

Quantitative real-time polymerase chain reaction, immunohistochemistry, enzyme-linked immunosorbent assay and Western blotting were used to assess gene and protein expression in nasal tissue extracts. Cells isolated from nasal tissues and peripheral blood mononuclear cells were characterized by flow cytometry. Local antibody production was measured in tissue extracts with a Bio-Plex assay. Additionally, changes in Hrd1 expression in response to specific inflammatory stimuli were measured in cultured dispersed polyp cells.

Results

Nasal polyps (NPs) from patients with eosinophilic CRSwNP (ECRS) had increased levels of Hrd1, B-cells and plasma cells compared with NPs from patients with non-eosinophilic CRSwNP (non-ECRS) or other control subjects (P < 0.05). The average Hrd1 levels in B-cells in NPs from ECRS patients were significantly higher than those from non-ECRS patients and control subjects (P < 0.05). NPs also contained significantly increased levels of several antibody isotypes compared with normal controls (P < 0.05). Interestingly, Hrd1 expression in cultured polyp cells from ECRS patients, but not non-ECRS patients, was significantly increased by interleukin-1?, lipopolysaccharide and Poly(I:C) stimulation, and inhibited by dexamethasone treatment (P < 0.05).

Conclusions

Differential Hrd1 expression and B-cell accumulation between the ECRS and non-ECRS subsets suggests that they can exhibit distinct pathogenic mechanisms and play important roles in NP.

SUBMITTER: Chen K

PROVIDER: S-EPMC6182200 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

Differential Hrd1 Expression and B-Cell Accumulation in Eosinophilic and Non-eosinophilic Chronic Rhinosinusitis With Nasal Polyps.

Chen Kun K Han Miaomiao M Tang Mengyao M Xie Yadong Y Lai Yuting Y Hu Xianting X Zhang Jia J Yang Jun J Li Huabin H

Allergy, asthma & immunology research 20181101 6

<h4>Purpose</h4>Hrd1 has recently emerged as a critical regulator of B-cells in autoimmune diseases. However, its role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) remains largely unexplored. This study aimed to examine Hrd1 expression and B-cell accumulation and their possible roles in CRSwNP.<h4>Methods</h4>Quantitative real-time polymerase chain reaction, immunohistochemistry, enzyme-linked immunosorbent assay and Western blotting were used to assess gene and prote ...[more]

PMID: 30306751

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Project description:Background: Alternative polyadenylation (APA) is emerging as a widespread mechanism of gene regulation. The usage of APA sites allows a single gene to encode multiple mRNA transcripts with different 3'-untranslated region (3'UTR) lengths. Many disease processes reflect the importance of the regulation of APA site switching. The objective of this study was to explore the profiling of tandem APA sites in nasal polyps compared with nasal uncinate process mucosa. Methods: Sequencing of APA sites (SAPAS) based on second-generation sequencing technology was undertaken to investigate the use of tandem APA sites and identify gene expression patterns in samples from the nasal polyps and nasal uncinate process mucosa of two patients with chronic rhinosinusitis with nasal polyps. The findings of the SAPAS analysis were validated via quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Results: First, the results showed a switching of 3'UTR lengths in nasal polyps compared with nasal uncinate process mucosa. From the two patients, 105 overlapping genes in the nasal polyps were switched to distal poly(A) sites, and 90 such genes were switched to proximal poly(A) sites. Several Gene Ontology terms were enriched in the list of genes with switched APA sites, including transcription regulation, cell cycle, apoptosis, and metabolism. Second, we detected genes that showed differential expression with at least a 3-fold difference between nasal polyp tissue and nasal uncinate process mucosa. Between the two sample types, 627 genes exhibited differential expression. The qRT-PCR results confirmed our SAPAS results. Conclusion: APA site-switching events of 3'UTRs are prevalent in nasal polyp tissue, and the regulation of gene expression mediated by APA may play an important role in the formation and persistence of nasal polyps. Our results may provide new insights into the possible pathophysiologic processes involved in nasal polyps. Investigate the use of tandem APA sites of 3'ends of mRNAs using second-generation sequencing technology.

Dataset Information

Differential Hrd1 Expression and B-Cell Accumulation in Eosinophilic and Non-eosinophilic Chronic Rhinosinusitis With Nasal Polyps.

Purpose

Methods

Results

Conclusions

Publications

Differential Hrd1 Expression and B-Cell Accumulation in Eosinophilic and Non-eosinophilic Chronic Rhinosinusitis With Nasal Polyps.

Similar Datasets

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