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Small RNA-Seq and real time rt-qPCR reveal islet miRNA released under stress conditions.
Islets 16:2392343 (2024)
Replacement of beta cells through transplantation is a potential therapeutic approach for individuals with pancreas removal or poorly controllable type 1 diabetes. However, stress and death of beta cells pose significant challenges. Circulating miRNA has emerged as potential biomarkers reflecting early beta cell stress and death, allowing for timely intervention. The aim of this study was to identify miRNAs as potential biomarkers for beta cell health. Literature review combined with small RNA sequencing was employed to select islet-enriched miRNA. The release of those miRNA was assessed by RT-qPCR in vivo, using a streptozotocin induced diabetes mouse model and in vitro, through mouse and human islets exposed to varying degrees of hypoxic and cytokine stressors. Utilizing the streptozotocin induced model, we identified 18 miRNAs out of 39 candidate islet-enriched miRNA to be released upon islet stress in vivo. In vitro analysis of culture supernatants from cytokine and/or hypoxia stressed islets identified the release of 45 miRNAs from mouse and 8 miRNAs from human islets. Investigation into the biological pathways targeted by the cytokine- and/or hypoxia-induced miRNA suggested the involvement of MAPK and PI3K-Akt signaling pathways in both mouse and human islets. We have identified miRNAs associated with beta cell health and stress. The findings allowed us to propose a panel of 47 islet-related human miRNA that is potentially valuable for application in clinical contexts of beta cell transplantation and presymptomatic early-stage type 1 diabetes.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Biomarker ; T1d ; Islet Beta Cell Stress ; Mirna ; Transplantation; Microrna Expression; Biomarker; Mir-375; Cancer; Transplantation; Regulators; Markers; Serum
ISSN (print) / ISBN
1938-2014
e-ISSN
1938-2022
Journal
Islets
Quellenangaben
Volume: 16,
Issue: 1,
Article Number: 2392343
Publisher
Landes Bioscience
Publishing Place
530 Walnut Street, Ste 850, Philadelphia, Pa 19106 Usa
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes Research (IDF)
Institute of Pancreatic Islet Research (IPI)
Institute of Pancreatic Islet Research (IPI)
Grants
German Ministry for Education and Research (BMBF)
Deutsche Forschungs Gesellschaft (DFG)
Deutsche Forschungs Gesellschaft (DFG)