Extracellular Vesicle MicroRNA That Are Involved in β-Thalassemia Complications

Levin, Carina; Koren, Ariel; Rebibo-Sabbah, Annie; Levin, Maya; Koifman, Naama; Brenner, Benjamin; Aharon, Anat

doi:10.3390/ijms22189760

Cited by 11 publications

(8 citation statements)

References 55 publications

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“…This suggests that elevating HIF1α levels can increase BHLHE40 expression. Moreover, HIF1α serves as a transcription factor for CD71, promoting its expression as well [ 41] . These ndings suggest that promoting HIF1α expression alone could concurrently stimulate BHLHE40 and CD71 expressions.…”

Section: Discussionmentioning

confidence: 99%

PDE6G inhibits the expression of CD71 in erythroid progenitor cells through the PDE6G/BHLHE40/miR144-3p/CD71 pathway, leading to red cell production obstacles and ultimately causing anemia in myelofibrosis

Wu,

Zhehan

2024

Preprint

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Myelofibrosis(MF) is a haematological malignancy. Most patients with MF will develop mild to moderate anemia. The MF-related anemia results from multifactorial factors. At present, the molecular mechanisms leading to MF-related anemia are still not fully understood. This study aimed to explore the role of PDE6G in MF-related anemia, verify its effect on the differentiation of erythroid progenitors, and reveal the molecular mechanism of action. This study examined PDE6G expression in bone marrow samples from Philadelphia chromosome-negative MPN and patients with MF without anemia, followed by mechanism studies using the HEL cell line (with JAK2V617F mutation) model and validation in human bone marrow specimens. We found that PDE6G expression was significantly higher in bone marrow samples from MF patients with anemia than in patients without anemia, and PDE6G inhibited the expression of CD71 in erythroid progenitors through the PDE6G/BHLHE40/miR-144-3p/CD71 pathway, leading to impaired erythroid production and ultimately myelofibrosis anemia. In conclusion, this study revealed the important mechanism of PDE6G in MF-related anemia, providing new ideas for research and treatment in this field, and is expected to provide a theoretical basis for the treatment of MF-related anemia.

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Section: Discussionmentioning

confidence: 99%

PDE6G inhibits the expression of CD71 in erythroid progenitor cells through the PDE6G/BHLHE40/miR144-3p/CD71 pathway, leading to red cell production obstacles and ultimately causing anemia in myelofibrosis

Wu,

Zhehan

2024

Preprint

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“…Was isolated from representative plasma samples (1 ml PPP) and EV pellets obtained from each study group. The miRNeasy isolation kit (Qiagen, Hilden, Germany) was used, with some modifications as previously described (Aharon et al, 2020;Levin et al, 2021). RNA concentration and quality were measured by a NanoDrop 2000 spectrophotometer (Thermo Fisher Scientific, Inc., Waltham, MA, USA).…”

Section: Rna Extractions and Mirna Screening 231 Ev Rnamentioning

confidence: 99%

Associations of maternal and placental extracellular vesicle miRNA with preeclampsia

Aharon

Rebibo-Sabbah

Ahmad

et al. 2023

Front. Cell Dev. Biol.

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Introduction: Gestational vascular complications (GVCs), including gestational hypertension and preeclampsia, are leading causes of maternal morbidity and mortality. Elevated levels of extracellular vesicles (EVs), in GVC have been linked to vascular injury. This study aims to characterize placental and circulating EV miRNA in GVCs, and explores the involvement of EV-miRNA in GVC, and whether they may be used to distinguish between placental and maternal pathologies.Methods: Blood samples were obtained from 15 non-pregnant (NP), 18 healthy-pregnant (HP), and 23 women with GVC during the third trimester. Placental sections were obtained after caesarian section. Platelet-poor-plasma (PPP) and EV pellets were characterized: EV size/concentration, protein content and miRNA expression were measured by nanoparticle tracking analysis, western blot, nano-string technology and RT-PCR. The effects of EVs on trophoblasts and EC miRNA expression were evaluated.Results: Higher EVs concentrations were observed in HP-PPP and GVC-PPP (p < 0.0001) compared to the NP-PPP. The concentration of large EVs (>100 nm) was higher in PPP and EV pellets of HP and GVC compared to the NP group. EV pellets of pregnant women demonstrated lower expression of exosomal markers CD63/CD81 compared to NP-EVs. GVC-EVs expressed more human placental lactogen (hPL) hormone than HP-EVs, reflecting their placental origin. Screening of miRNAs in EV pellets and in PPP identified certain miRNAs that were highly expressed only in EVs pellets of the HP (13%) and GVC groups (15%), but not in the NP group. Differences were detected in the expression of hsa-miR-16-5p, hsa-miR-210, and hsa-miR-29b-3p. The expression of hsa-miR-16-5p and hsa-miR-210 was low in EV pellets obtained from NP, higher in HP-EVs, and significantly lower in GVC-EVs. Except for hsa-miR-29b-3p, which was upregulated in GVC, no significant differences were found in the levels of other miRNAs in placental sections. Exposure to GVC-EVs resulted in higher expression of hsa-miR-29b-3p compared to cells exposed to HP-EVs in villous trophoblasts, but not in EC.Conclusion: Expression of hsa-miR-16-5p and hsa-miR-210 reflects maternal pathophysiological status, while hsa-miR-29b-3p reflects placental status. These findings suggest that EV-miRNA are involved in GVC, and that they may be used to distinguish between pathologies of placental and maternal origins in preeclampsia.

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“…Only a few studies have described exosomes or microvesicles from hemoglobinopathy adult patients [ 174 , 175 , 176 , 177 , 178 , 179 ]. In addition, most of these studies examined the role of microparticles in circulation from adults with Beta-thalassemia/Hb E disease in relation to the hypercoagulable state.…”

Section: Placenta-derived Evs As Hb Bart’s Liquid Biopsy: Challenges ...mentioning

confidence: 99%

Placenta-Derived Extracellular Vesicles in Pregnancy Complications and Prospects on a Liquid Biopsy for Hemoglobin Bart’s Disease

Chaemsaithong

Luewan

Taweevisit

et al. 2023

IJMS

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Extracellular vesicles (EVs) are nano-scaled vesicles released from all cell types into extracellular fluids and specifically contain signature molecules of the original cells and tissues, including the placenta. Placenta-derived EVs can be detected in maternal circulation at as early as six weeks of gestation, and their release can be triggered by the oxygen level and glucose concentration. Placental-associated complications such as preeclampsia, fetal growth restriction, and gestational diabetes have alterations in placenta-derived EVs in maternal plasma, and this can be used as a liquid biopsy for the diagnosis, prediction, and monitoring of such pregnancy complications. Alpha-thalassemia major (“homozygous alpha-thalassemia-1”) or hemoglobin Bart’s disease is the most severe form of thalassemia disease, and this condition is lethal for the fetus. Women with Bart’s hydrops fetalis demonstrate signs of placental hypoxia and placentomegaly, thereby placenta-derived EVs provide an opportunity for a non-invasive liquid biopsy of this lethal condition. In this article, we introduced clinical features and current diagnostic markers of Bart’s hydrops fetalis, extensively summarize the characteristics and biology of placenta-derived EVs, and discuss the challenges and opportunities of placenta-derived EVs as part of diagnostic tests for placental complications focusing on Bart’s hydrop fetalis.

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Extracellular Vesicle MicroRNA That Are Involved in β-Thalassemia Complications

Cited by 11 publications

References 55 publications

PDE6G inhibits the expression of CD71 in erythroid progenitor cells through the PDE6G/BHLHE40/miR144-3p/CD71 pathway, leading to red cell production obstacles and ultimately causing anemia in myelofibrosis

PDE6G inhibits the expression of CD71 in erythroid progenitor cells through the PDE6G/BHLHE40/miR144-3p/CD71 pathway, leading to red cell production obstacles and ultimately causing anemia in myelofibrosis

Associations of maternal and placental extracellular vesicle miRNA with preeclampsia

Placenta-Derived Extracellular Vesicles in Pregnancy Complications and Prospects on a Liquid Biopsy for Hemoglobin Bart’s Disease

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