التفاصيل البيبلوغرافية
| العنوان: |
Detection of Antiviral Tissue Responses and Increased Cell Stress in the Pancreatic Islets of Newly Diagnosed Type 1 Diabetes Patients: Results From the DiViD Study |
| المؤلفون: |
Krogvold, Lars, Leete, Pia, Mynarek, Ida M., Russell, Mark A., Gerling, Ivan C., Lenchik, Nataliya I., Mathews, Clayton, Richardson, Sarah J., Morgan, Noel G., Dahl-Jørgensen, Knut |
| المساهمون: |
Helse Sør-Øst RHF, Juvenile Diabetes Research Foundation United States of America, Seventh Framework Programme |
| المصدر: |
Frontiers in Endocrinology ; volume 13 ; ISSN 1664-2392 |
| بيانات النشر: |
Frontiers Media SA |
| سنة النشر: |
2022 |
| المجموعة: |
Frontiers (Publisher - via CrossRef) |
| مصطلحات موضوعية: |
Endocrinology, Diabetes and Metabolism |
| الوصف: |
Aims/hypothesis The Diabetes Virus Detection (DiViD) study has suggested the presence of low-grade enteroviral infection in pancreatic tissue collected from six of six live adult patients newly diagnosed with type 1 diabetes. The present study aimed to compare the gene and protein expression of selected virally induced pathogen recognition receptors and interferon stimulated genes in islets from these newly diagnosed type 1 diabetes (DiViD) subjects vs age-matched non-diabetic (ND) controls. Methods RNA was extracted from laser-captured islets and Affymetrix Human Gene 2.0 ST arrays used to obtain gene expression profiles. Lists of differentially expressed genes were subjected to a data-mining pipeline searching for enrichment of canonical pathways, KEGG pathways, Gene Ontologies, transcription factor binding sites and other upstream regulators. In addition, the presence and localisation of specific viral response proteins (PKR, MxA and MDA5) were examined by combined immunofluorescent labelling in sections of pancreatic tissue. Results The data analysis and data mining process revealed a significant enrichment of gene ontologies covering viral reproduction and infectious cycles; peptide translation, elongation and initiation, as well as oxidoreductase activity. Enrichment was identified in the KEGG pathways for oxidative phosphorylation; ribosomal and metabolic activity; antigen processing and presentation and in canonical pathways for mitochondrial dysfunction, oxidative phosphorylation and EIF2 signaling. Protein Kinase R (PKR) expression did not differ between newly diagnosed type 1 diabetes and ND islets at the level of total RNA, but a small subset of β-cells displayed markedly increased PKR protein levels. These PKR+ β-cells correspond to those previously shown to contain the viral protein, VP1. RNA encoding MDA5 was increased significantly in newly diagnosed type 1 diabetes islets, and immunostaining of MDA5 protein was seen in α- and certain β-cells in both newly diagnosed type 1 diabetes and ND islets, ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
unknown |
| DOI: |
10.3389/fendo.2022.881997 |
| DOI: |
10.3389/fendo.2022.881997/full |
| الإتاحة: |
https://doi.org/10.3389/fendo.2022.881997Test |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.26F1FFE1 |
| قاعدة البيانات: |
BASE |
