Changes in Gene Expression of Selected Genes in Patients with Type 1 Diabetes and Pancreas Transplant in Peripheral Blood

Klak, Marta; Urban, Sabina; Gomółka, Magdalena; Cichoń, Justyna; Ambrożkiewicz, Filip; Berman, Andrzej; Serwańska-Świętek, Marta; Wszoła, Michał

doi:10.1016/j.transproceed.2019.04.086

Cited by 3 publications

(1 citation statement)

References 16 publications

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“…A number of gene expression analysis studies have previously been performed to examine disease pathogenesis in T1D. The majority of studies, however, have been carried out using peripheral blood samples of AA+ at-risk and early onset T1D patients, while relatively few have been performed in the pancreata of these individuals, where insulitis, and islet destruction occur (66)(67)(68)(69)(70)(71)(72). This is partly due to the lack of pancreas samples available for study, and the difficulty in extracting high-quality RNA from these tissues.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Analysis of the Pre-Diabetic Pancreas to Identify Pathogenic Mechanisms and Biomarkers of Type 1 Diabetes

et al. 2020

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Type 1 Diabetes (T1D) occurs as a result of the autoimmune destruction of pancreatic β-cells by self-reactive T cells. The etiology of this disease is complex and difficult to study due to a lack of disease-relevant tissues from pre-diabetic individuals. In this study, we performed gene expression analysis on human pancreas tissues obtained from the Network of Pancreatic Organ Donors with Diabetes (nPOD), and showed that 155 genes were differentially expressed by ≥2-fold in the pancreata of autoantibody-positive (AA+) at-risk individuals compared to healthy controls. Only 48 of these genes remained changed by ≥2-fold in the pancreata of established T1D patients. Pathway analysis of these genes showed a significant association with various immune pathways. We were able to validate the differential expression of eight disease-relevant genes by QPCR analysis: A significant upregulation of CADM2, and downregulation of TRPM5, CRH, PDK4, ANGPL4, CLEC4D, RSG16, and FCGR2B was confirmed in the pancreata of AA+ individuals versus controls. Studies have already implicated FCGR2B in the pathogenesis of disease in non-obese diabetic (NOD) mice. Here we showed that CADM2, TRPM5, PDK4, and ANGPL4 were similarly changed in the pancreata of pre-diabetic 12-week-old NOD mice compared to NOD.B10 controls, suggesting a possible role for these genes in the pathogenesis of both T1D and NOD disease. The loss of the leukocyte-specific gene, FCGR2B, in the pancreata of AA+ individuals, is particularly interesting, as it may serve as a potential whole blood biomarker of disease progression. To test this, we quantified FCGR2B expression in peripheral blood samples of T1D patients, and AA+ and AA- first-degree relatives of T1D patients enrolled in the TrialNet Pathway to Prevention study. We showed that FCGR2B was significantly reduced in the peripheral blood of AA+ individuals compared to AA- controls. Together, these findings demonstrate that gene expression analysis of pancreatic tissue and peripheral blood samples can be used to identify disease-relevant genes and pathways and potential biomarkers of disease progression in T1D.

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Section: Discussionmentioning

confidence: 99%

Gene Expression Analysis of the Pre-Diabetic Pancreas to Identify Pathogenic Mechanisms and Biomarkers of Type 1 Diabetes

et al. 2020

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Astragaloside IV as Potential Antioxidant Against Diabetic Ketoacidosis in Juvenile Mice Through Activating JNK/Nrf2 Signaling Pathway

Deng

2020

Archives of Medical Research

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MicroRNAs and Diabetes Mellitus Type 1

Bahreini

Rayzan

Rezaei

2022

CDR

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: Type 1 diabetes mellitus is a multifactorial, progressive, autoimmune disease with a strong genetic feature that can affect multiple organs, including kidney, eyes, and nerves. Early detection of type 1 diabetes can help critically to avoid serious damages to these organs. MicroRNAs are small RNA molecules that act in post-transcriptional gene regulation by attaching to the complementary sequence in the 3'-untranslated region of their target genes. Alterations in the expression of microRNA coding genes are extensively reported in several diseases such as type 1 diabetes. Presenting non-invasive biomarkers for early detection of type 1 diabetes by quantifying microRNAs gene expression level can be an influential step in biotechnology and medicine. This review discusses the area of microRNAs dysregulation in type 1 diabetes and affected molecular mechanisms involved in pancreatic islet cells formation and dysregulation in the expression of inflammatory elements as well as pro-inflammatory cytokines.

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Changes in Gene Expression of Selected Genes in Patients with Type 1 Diabetes and Pancreas Transplant in Peripheral Blood

Cited by 3 publications

References 16 publications

Gene Expression Analysis of the Pre-Diabetic Pancreas to Identify Pathogenic Mechanisms and Biomarkers of Type 1 Diabetes

Gene Expression Analysis of the Pre-Diabetic Pancreas to Identify Pathogenic Mechanisms and Biomarkers of Type 1 Diabetes

Astragaloside IV as Potential Antioxidant Against Diabetic Ketoacidosis in Juvenile Mice Through Activating JNK/Nrf2 Signaling Pathway

MicroRNAs and Diabetes Mellitus Type 1

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