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Volume 22
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Article

Extracellular Vesicle MicroRNA That Are Involved in β-Thalassemia Complications

by
Carina Levin
1,2,*,
Ariel Koren
1,2,
Annie Rebibo-Sabbah
3,
Maya Levin
4,
Na’ama Koifman
5,
Benjamin Brenner
2,3 and
Anat Aharon
2,3,4
1
Pediatric Hematology Unit, Emek Medical Center, Afula 1834111, Israel
2
Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3109601, Israel
3
Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa 3109601, Israel
4
The Hematology Research Laboratory, Tel Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel
5
Department of Chemical Engineering and the Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa 3200003, Israel
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(18), 9760; https://doi.org/10.3390/ijms22189760
Submission received: 30 July 2021 / Revised: 6 September 2021 / Accepted: 6 September 2021 / Published: 9 September 2021
(This article belongs to the Special Issue The Role of Exosomes in Health and Disease)
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Abstract

Beta thalassemia major (βT) is a hereditary anemia characterized by transfusion-dependency, lifelong requirement of chelation, and organ dysfunction. MicroRNA (miRNA) can be packed into extracellular vesicles (EVs) that carry them to target cells. We explored EV-miRNA in βT and their pathophysiologic role. Circulating EVs were isolated from 35 βT-patients and 15 controls. EV miRNA was evaluated by nano-string technology and real-time quantitative polymerase chain reaction (RT-qPCR). We explored effects of EVs on cell culture proliferation, apoptosis, and signal transduction. Higher amounts of small EV (exosomes) were found in patients than in controls. The expression of 21 miRNA was > two-fold higher, and of 17 miRNA < three-fold lower in βT-EVs than control-EVs. RT-qPCR confirmed differential expression of six miRNAs in βT, particularly miR-144-3p, a regulator of erythropoiesis. Exposure of endothelial, liver Huh7, and pancreatic 1.1B4 cells to βT-EVs significantly reduced cell viability and increased cell apoptosis. βT-EV-induced endothelial cell apoptosis involved the MAPK/JNK signal-transduction pathway. In contrast, splenectomized βT-EVs induced proliferation of bone marrow mesenchymal stem cells (BM-MSC). In summary, the miR-144-3p was strongly increased; βT-EVs induced apoptosis and decreased endothelial, pancreatic, and liver cell survival while supporting BM-MSC proliferation. These mechanisms may contribute to βT organ dysfunction and complications.
Keywords: β-thalassemia major; extracellular vesicles (EVs); microRNA (miRNA); signal-transduction β-thalassemia major; extracellular vesicles (EVs); microRNA (miRNA); signal-transduction

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MDPI and ACS Style

Levin, C.; Koren, A.; Rebibo-Sabbah, A.; Levin, M.; Koifman, N.; Brenner, B.; Aharon, A. Extracellular Vesicle MicroRNA That Are Involved in β-Thalassemia Complications. Int. J. Mol. Sci. 2021, 22, 9760. https://doi.org/10.3390/ijms22189760

AMA Style

Levin C, Koren A, Rebibo-Sabbah A, Levin M, Koifman N, Brenner B, Aharon A. Extracellular Vesicle MicroRNA That Are Involved in β-Thalassemia Complications. International Journal of Molecular Sciences. 2021; 22(18):9760. https://doi.org/10.3390/ijms22189760

Chicago/Turabian Style

Levin, Carina, Ariel Koren, Annie Rebibo-Sabbah, Maya Levin, Na’ama Koifman, Benjamin Brenner, and Anat Aharon. 2021. "Extracellular Vesicle MicroRNA That Are Involved in β-Thalassemia Complications" International Journal of Molecular Sciences 22, no. 18: 9760. https://doi.org/10.3390/ijms22189760

APA Style

Levin, C., Koren, A., Rebibo-Sabbah, A., Levin, M., Koifman, N., Brenner, B., & Aharon, A. (2021). Extracellular Vesicle MicroRNA That Are Involved in β-Thalassemia Complications. International Journal of Molecular Sciences, 22(18), 9760. https://doi.org/10.3390/ijms22189760

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