Extracellular Vesicle MicroRNA That Are Involved in β-Thalassemia Complications
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 pathophysiologi...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2021-09-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/22/18/9760 |
id |
doaj-7d28e6cb6a914d3fbb7a4234d842f7c8 |
---|---|
record_format |
Article |
spelling |
doaj-7d28e6cb6a914d3fbb7a4234d842f7c82021-09-26T00:22:45ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-01229760976010.3390/ijms22189760Extracellular Vesicle MicroRNA That Are Involved in β-Thalassemia ComplicationsCarina Levin0Ariel Koren1Annie Rebibo-Sabbah2Maya Levin3Na’ama Koifman4Benjamin Brenner5Anat Aharon6Pediatric Hematology Unit, Emek Medical Center, Afula 1834111, IsraelPediatric Hematology Unit, Emek Medical Center, Afula 1834111, IsraelDepartment of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa 3109601, IsraelThe Hematology Research Laboratory, Tel Aviv Sourasky Medical Center, Tel Aviv 6423906, IsraelDepartment of Chemical Engineering and the Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa 3200003, IsraelBruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3109601, IsraelBruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3109601, IsraelBeta 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.https://www.mdpi.com/1422-0067/22/18/9760β-thalassemia majorextracellular vesicles (EVs)microRNA (miRNA)signal-transduction |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Carina Levin Ariel Koren Annie Rebibo-Sabbah Maya Levin Na’ama Koifman Benjamin Brenner Anat Aharon |
spellingShingle |
Carina Levin Ariel Koren Annie Rebibo-Sabbah Maya Levin Na’ama Koifman Benjamin Brenner Anat Aharon Extracellular Vesicle MicroRNA That Are Involved in β-Thalassemia Complications International Journal of Molecular Sciences β-thalassemia major extracellular vesicles (EVs) microRNA (miRNA) signal-transduction |
author_facet |
Carina Levin Ariel Koren Annie Rebibo-Sabbah Maya Levin Na’ama Koifman Benjamin Brenner Anat Aharon |
author_sort |
Carina Levin |
title |
Extracellular Vesicle MicroRNA That Are Involved in β-Thalassemia Complications |
title_short |
Extracellular Vesicle MicroRNA That Are Involved in β-Thalassemia Complications |
title_full |
Extracellular Vesicle MicroRNA That Are Involved in β-Thalassemia Complications |
title_fullStr |
Extracellular Vesicle MicroRNA That Are Involved in β-Thalassemia Complications |
title_full_unstemmed |
Extracellular Vesicle MicroRNA That Are Involved in β-Thalassemia Complications |
title_sort |
extracellular vesicle microrna that are involved in β-thalassemia complications |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-09-01 |
description |
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. |
topic |
β-thalassemia major extracellular vesicles (EVs) microRNA (miRNA) signal-transduction |
url |
https://www.mdpi.com/1422-0067/22/18/9760 |
work_keys_str_mv |
AT carinalevin extracellularvesiclemicrornathatareinvolvedinbthalassemiacomplications AT arielkoren extracellularvesiclemicrornathatareinvolvedinbthalassemiacomplications AT annierebibosabbah extracellularvesiclemicrornathatareinvolvedinbthalassemiacomplications AT mayalevin extracellularvesiclemicrornathatareinvolvedinbthalassemiacomplications AT naamakoifman extracellularvesiclemicrornathatareinvolvedinbthalassemiacomplications AT benjaminbrenner extracellularvesiclemicrornathatareinvolvedinbthalassemiacomplications AT anataharon extracellularvesiclemicrornathatareinvolvedinbthalassemiacomplications |
_version_ |
1717366332072132608 |