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Article

The MicroRNA Landscape of Acute Beta Cell Destruction in Type 1 Diabetic Recipients of Intraportal Islet Grafts

1
Diabetes Research Center, Brussels Free University (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium
2
Department of Laboratory Medicine, Molecular Diagnostics Unit, AZ Delta General Hospital, 8800 Roeselare, Belgium
3
Department of Biomolecular Medicine, Ghent University, 9000 Gent, Belgium
4
Diabetes Research Institute, Università Vita-Salute San Raffaele, 20132 Milan, Italy
5
Center for Medical Genetics, University Hospital Ghent (UZ Gent), De Pintelaan 185, 9000 Ghent, Belgium
*
Author to whom correspondence should be addressed.
Academic Editors: Md Shahidul Islam and Michael E. Boulton
Cells 2021, 10(7), 1693; https://doi.org/10.3390/cells10071693
Received: 4 May 2021 / Revised: 16 June 2021 / Accepted: 24 June 2021 / Published: 4 July 2021
(This article belongs to the Special Issue Signal Transduction in the Islets of Langerhans)
Ongoing beta cell death in type 1 diabetes (T1D) can be detected using biomarkers selectively discharged by dying beta cells into plasma. microRNA-375 (miR-375) ranks among the top biomarkers based on studies in animal models and human islet transplantation. Our objective was to identify additional microRNAs that are co-released with miR-375 proportionate to the amount of beta cell destruction. RT-PCR profiling of 733 microRNAs in a discovery cohort of T1D patients 1 h before/after islet transplantation indicated increased plasma levels of 22 microRNAs. Sub-selection for beta cell selectivity resulted in 15 microRNAs that were subjected to double-blinded multicenter analysis. This led to the identification of eight microRNAs that were consistently increased during early graft destruction: besides miR-375, these included miR-132/204/410/200a/429/125b, microRNAs with known function and enrichment in beta cells. Their potential clinical translation was investigated in a third independent cohort of 46 transplant patients by correlating post-transplant microRNA levels to C-peptide levels 2 months later. Only miR-375 and miR-132 had prognostic potential for graft outcome, and none of the newly identified microRNAs outperformed miR-375 in multiple regression. In conclusion, this study reveals multiple beta cell-enriched microRNAs that are co-released with miR-375 and can be used as complementary biomarkers of beta cell death. View Full-Text
Keywords: beta cell; type 1 diabetes; islet transplantation; biomarkers; microRNA beta cell; type 1 diabetes; islet transplantation; biomarkers; microRNA
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MDPI and ACS Style

Martens, G.A.; Stangé, G.; Piemonti, L.; Anckaert, J.; Ling, Z.; Pipeleers, D.G.; Gorus, F.K.; Mestdagh, P.; De Smet, D.; Vandesompele, J.; Keymeulen, B.; Roels, S. The MicroRNA Landscape of Acute Beta Cell Destruction in Type 1 Diabetic Recipients of Intraportal Islet Grafts. Cells 2021, 10, 1693. https://doi.org/10.3390/cells10071693

AMA Style

Martens GA, Stangé G, Piemonti L, Anckaert J, Ling Z, Pipeleers DG, Gorus FK, Mestdagh P, De Smet D, Vandesompele J, Keymeulen B, Roels S. The MicroRNA Landscape of Acute Beta Cell Destruction in Type 1 Diabetic Recipients of Intraportal Islet Grafts. Cells. 2021; 10(7):1693. https://doi.org/10.3390/cells10071693

Chicago/Turabian Style

Martens, Geert A., Geert Stangé, Lorenzo Piemonti, Jasper Anckaert, Zhidong Ling, Daniel G. Pipeleers, Frans K. Gorus, Pieter Mestdagh, Dieter De Smet, Jo Vandesompele, Bart Keymeulen, and Sarah Roels. 2021. "The MicroRNA Landscape of Acute Beta Cell Destruction in Type 1 Diabetic Recipients of Intraportal Islet Grafts" Cells 10, no. 7: 1693. https://doi.org/10.3390/cells10071693

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