MicroRNA profiling in bronchial biopsies identifies altered expression in asthma and high levels of allergen-modulated epithelial microRNAs

Epithelial cells form a tight barrier against environmental stimuli via tight junctions (TJs) and adherence junctions (AJs). Defects in TJ and AJ proteins may cause changes in epithelial morphology and integrity and potentially lead to faster trafficking of inflammatory cells through the epithelium. Bronchial epithelial fragility has been reported in asthmatic patients, but little is known about the expression of TJ and AJ proteins in asthma. We studied epithelial expression of zonula occludens-1 (ZO-1) and AJ proteins E-cadherin, α-catenin, and β-catenin in bronchial biopsies from nonatopic nonasthmatic (healthy) subjects (n = 14), and stable atopic asthmatic subjects (n = 22) at baseline conditions. Immunostaining for these proteins was semi-quantified for separate cellular compartments. E-cadherin, α-catenin and β-catenin were present in the cellular membrane and less in the cytoplasm. Only β-catenin was present in the nucleus in agreement with its potential function as transcription factor. ZO-1 was present in the apicolateral membrane of superficial cells. α-Catenin expression was significantly lower in subjects with asthma than without and correlated inversely with numbers of eosinophils within the epithelium. ZO-1 and E-cadherin expression were significantly lower in asthmatic than in nonasthmatic subjects. Expression of β-catenin was not different. Our results suggest that the lower epithelial α-catenin, E-cadherin and (or) ZO-1 expression in patients with atopic asthma contributes to a defective airway epithelial barrier and a higher influx of eosinophils in the epithelium.

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Detection of SARS-CoV-2 infection by microRNA profiling of the upper respiratory tract

10.21203/rs.3.rs-907655/v1 ◽

2021 ◽

Author(s):

Ryan Farr ◽

Christina Rootes ◽

John Stenos ◽

Chwan Hong Foo ◽

Christopher Cowled ◽

...

Keyword(s):

Negative Regulator ◽

Supervised Machine Learning ◽

Minimally Invasive Procedures ◽

Upper Respiratory Tract ◽

Mirna Signature ◽

Invasive Procedures ◽

Altered Expression ◽

Microrna Profiling ◽

Upper Respiratory ◽

Learning Analysis

Abstract Host biomarkers are increasingly being considered as tools for improved COVID-19 detection and prognosis. We recently profiled circulating host-encoded microRNA (miRNAs) during SARS-CoV-2 infection, revealing a signature that classified COVID-19 cases with 99.9% accuracy. Here we sought to develop a signature suited for clinical application by analyzing specimens collected using minimally invasive procedures. Eight miRNAs displayed altered expression in anterior nasal tissues from COVID-19 patients, with miR-142-3p, a negative regulator of interleukin-6 (IL-6) production, the most strongly upregulated. Supervised machine learning analysis revealed that a three-miRNA signature (miR-30c-2-3p, miR-628-3p and miR-93-5p) independently classifies COVID-19 cases with 100 % accuracy. This study further defines the host miRNA response to SARS-CoV-2 infection and identifies candidate biomarkers for improved COVID-19 detection.

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MicroRNA Profiling in Bronchial Biopsies of Asthma Patients

10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a1059 ◽

2020 ◽

Author(s):

M.P. Roffel ◽

I.M. Boudewijn ◽

C.J. Vermeulen ◽

A. van Oosterhout ◽

K. Affleck ◽

...

Keyword(s):

Microrna Profiling ◽

Asthma Patients ◽

Bronchial Biopsies

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Neutrophil transmigration in inflammatory bowel disease is associated with altered expression of intercellular junction proteins

Gastroenterology ◽

10.1016/s0016-5085(01)80927-6 ◽

2001 ◽

Vol 120 (5) ◽

pp. A187-A187 ◽

Cited By ~ 1

Author(s):

T KUCHARZIK ◽

S WALSH ◽

J CHEN ◽

C PARKOS ◽

A NUSRAT

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Intercellular Junction ◽

Altered Expression ◽

Inflammatory Bowel ◽

Junction Proteins

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The Oral Intake of Organic Germanium, Ge-132, Elevates α-Tocopherol Levels in the Plas-ma and Modulates Hepatic Gene Expression Profiles to Promote Immune Activation in Mice

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000205 ◽

2014 ◽

Vol 84 (3-4) ◽

pp. 0183-0195 ◽

Cited By ~ 12

Author(s):

Takashi Nakamura ◽

Tomoya Takeda ◽

Yoshihiko Tokuji

Keyword(s):

Gene Expression ◽

Immune Activation ◽

Expression Profiles ◽

Water Soluble ◽

Alpha Tocopherol ◽

Hepatic Gene Expression ◽

Tocopherol Concentration ◽

Altered Expression ◽

Atp Production ◽

Transfer Protein

The common water-soluble organic germanium compound poly-trans-[(2-carboxyethyl) germasesquioxane] (Ge-132) exhibits activities related to immune responses and antioxidant induction. In this study, we evaluated the antioxidative effect of dietary Ge-132 in the plasma of mice. Male ICR mice (seven mice per group) received an AIN-76 diet with 0.05 % Ge-132; three groups received the Ge-132-containing diet for 0, 1 or 4 days. The plasma alpha-tocopherol (α-tocopherol) concentration increased from 6.85 to 9.60 μg/ml after 4 days of Ge-132 intake (p < 0.05). We evaluated the changes in hepatic gene expression related to antioxidative activity as well as in the entire expression profile after one day of Ge-132 intake, using DNA microarray technology. We identified 1,220 genes with altered expression levels greater than 1.5-fold (increased or decreased) as a result of Ge-132 intake, and α-tocopherol transfer protein (Ttpa) gene expression was increased 1.62-fold. Immune activation was identified as the category with the most changes (containing 60 Gene Ontology (GO) term biological processes (BPs), 41 genes) via functional clustering analysis of altered gene expression. Ge-132 affected genes in clusters related to ATP production (22 GO term BPs, 21 genes), lipid metabolism (4 GO term BPs, 38 genes) and apoptosis (5 GO term BPs). Many GO term BPs containing these categories were significantly affected by the Ge-132 intake. Oral Ge-132 intake may therefore have increased plasma α-tocopherol levels by up-regulating α-tocopherol transfer protein (Ttpa) gene expression.

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Altered expression of Ca2+ binding proteins in FRTL-5 clones expressing mutant TSH receptors

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-2007-972277 ◽

2007 ◽

Vol 115 (S 1) ◽

Author(s):

S Lorenz ◽

M Eszlinger ◽

D Führer ◽

K Krohn

Keyword(s):

Binding Proteins ◽

Altered Expression

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E-cadherin-catenin complex in the rat ovary: cell-specific expression during folliculogenesis and luteal formation

Reproduction ◽

10.1530/reprod/118.2.375 ◽

2000 ◽

pp. 375-385 ◽

Cited By ~ 10

Author(s):

K Sundfeldt ◽

Y Piontkewitz ◽

H Billig ◽

L Hedin

Keyword(s):

Granulosa Cells ◽

Interstitial Cells ◽

Ovary Cell ◽

Beta Catenin ◽

Oestrogen Treatment ◽

Altered Expression ◽

Preantral Follicles ◽

Rat Ovary ◽

E Cadherin ◽

Cell Cell

The cadherins and their cytoplasmic counterparts, the catenins, form the adherens junctions, which are of importance for tissue integrity and barrier functions. The development and maturation of the ovarian follicle is characterized by structural changes, which require altered expression or function of the components involved in cell-cell contacts. The present study examined the cell-specific localization and temporal expression of epithelial cadherin (E-cadherin) and alpha- and beta-catenin during follicular development, ovulation and corpus luteum formation in the immature gonadotrophin- and oestrogen-stimulated rat ovary. Immunohistochemistry and immunoblotting demonstrated the expression of E-cadherin in theca and interstitial cells of immature ovaries before and after injection of equine chorionic gonadotrophin (eCG). E-cadherin was not detected in granulosa cells, except in the preantral follicles located to the inner region of the ovary. The content of E-cadherin in theca and interstitial cells decreased after an ovulatory dose of hCG. Granulosa cells of apoptotic follicles did not express E-cadherin. Oestrogen treatment (diethylstilboestrol) of immature rats for up to 3 days did not result in a measurable expression of E-cadherin in granulosa cells. alpha- and beta-catenin were expressed in all ovarian compartments. The concentration of beta-catenin was constant during the follicular phase, whereas the content of alpha-catenin decreased in granulosa cells after treatment with diethylstilboestrol or hCG. The expression of alpha-catenin was also reduced in theca and interstitial cells after hCG. alpha- and beta-catenin were present in most ovarian cells at all stages of folliculogenesis. Therefore, the catenins have the potential to associate with different members of the cadherin family and to participate in the regulation of cytoskeletal structures and intracellular signalling. The restricted expression of E-cadherin in granulosa cells of preantral follicles indicates a role in the recruitment of these follicles to subsequent cycles. The specific decrease of alpha-catenin in granulosa cells and the reduction of both alpha-catenin and E-cadherin in theca cells of ovulatory follicles might reflect some of the molecular changes in cell-cell adhesion associated with ovulation and luteinization.

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MicroRNAs and their role in hematological malignant diseases

Orvosi Hetilap ◽

10.1556/oh.2012.29511 ◽

2012 ◽

Vol 153 (52) ◽

pp. 2051-2059 ◽

Cited By ~ 8

Author(s):

Zsuzsanna Gaál ◽

Éva Oláh

Keyword(s):

Target Genes ◽

Lymphoblastic Leukemia ◽

Cancer Tissue ◽

Altered Expression ◽

Diagnosis And Prognosis ◽

Oncologic Patients ◽

Different Types ◽

Non Coding Rnas ◽

Success Of Treatment ◽

Posttranscriptional Level

MicroRNAs are a class of small non-coding RNAs regulating gene expression at posttranscriptional level. Their target genes include numerous regulators of cell cycle, cell proliferation as well as apoptosis. Therefore, they are implicated in the initiation and progression of cancer, tissue invasion and metastasis formation as well. MicroRNA profiles supply much information about both the origin and the differentiation state of tumours. MicroRNAs also have a key role during haemopoiesis. An altered expression level of those have often been observed in different types of leukemia. There are successful attempts to apply microRNAs in the diagnosis and prognosis of acute lymphoblastic leukemia and acute myeloid leukemia. Measurement of the expression levels may help to predict the success of treatment with different kinds of chemotherapeutic drugs. MicroRNAs are also regarded as promising therapeutic targets, and can contribute to a more personalized therapeutic approach in haemato-oncologic patients. Orv. Hetil., 2012, 153, 2051–2059.

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