JAK2V617F-Positive Endothelial Cells Induce Apoptosis and Release JAK2V617F-Positive Microparticles
Objective: Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) have a high propensity for thrombosis, which has been attributed to increased blood counts, endothelial cell (EC) dysfunction, and inflammation. The presence of the JAK2V617F mutation in the ECs of MPN patients has been...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Galenos Publishing House
2022-02-01
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| Series: | Turkish Journal of Hematology |
| Subjects: | |
| Online Access: | https://jag.journalagent.com/z4/download_fulltext.asp?pdir=tjh&un=TJH-57355 |
| _version_ | 1797916975843770368 |
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| author | Hilal Hekimoğlu Selin Fulya Toprak Selçuk Sözer |
| author_facet | Hilal Hekimoğlu Selin Fulya Toprak Selçuk Sözer |
| author_sort | Hilal Hekimoğlu |
| collection | DOAJ |
| description | Objective: Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) have a high propensity for thrombosis, which has been attributed to increased blood counts, endothelial cell (EC) dysfunction, and inflammation. The presence of the JAK2V617F mutation in the ECs of MPN patients has been confirmed, but the consequences of EC involvement by JAK2V617F in the pathogenesis of thrombosis are unclear. Endothelial microparticles (EMPs) released from ECs play an important role in endothelial dysfunction and also in the intercellular exchange of biological signals and information. Several studies have revealed that patients with JAK2V617F and a thrombosis history have increased numbers of MPs in their circulation. Materials and Methods: The current study utilized a lentiviral transduction model of JAK2 wild type (JAK2wt) or JAK2V617F encoding green fluorescent protein (GFP) into human umbilical vein ECs to determine the effect of JAK2V617F on ECs. EC infected with JAK2V617F, JAK2WT, and only-GFP were tested after two days of culture. Results: The proteins of ECs that potentially play a role in the development of thrombosis, including endothelial protein C receptor, thrombomodulin, and tissue factor, were detected by flow cytometry analysis with no statistical significance. Increased annexin-V uptake of JAK2V617F and JAK2wt ECs compared to GFP-alone ECs was detected. The EMP production in the supernatants of the EC culture was investigated. Genotyping of the EMPs revealed the presence of genomic DNA and RNA fragments in EMP cargos. JAK2V617F-positive DNA was detected in EMPs released from JAK2V617F-infected ECs and EMPs were shown to carry the genotype of the cell of origin. Conclusion: JAK2V617F-positive EMPs were shown for the first time in the literature. This novel research provides the first evidence that EMPs might regulate neighboring and distant cells via their cargo materials. Thus, the direct effect of JAK2V617F on ECs and their functions suggests that different mechanisms might play a role in the pathogenesis of thrombosis in MPNs. |
| first_indexed | 2024-04-10T13:05:56Z |
| format | Article |
| id | doaj.art-4bcfca2bc0bd4e88a25867c3e6f46872 |
| institution | Directory Open Access Journal |
| issn | 1308-5263 |
| language | English |
| last_indexed | 2024-04-10T13:05:56Z |
| publishDate | 2022-02-01 |
| publisher | Galenos Publishing House |
| record_format | Article |
| series | Turkish Journal of Hematology |
| spelling | doaj.art-4bcfca2bc0bd4e88a25867c3e6f468722023-02-15T16:12:58ZengGalenos Publishing HouseTurkish Journal of Hematology1308-52632022-02-01391132110.4274/tjh.galenos.2021.2021.0607TJH-57355JAK2V617F-Positive Endothelial Cells Induce Apoptosis and Release JAK2V617F-Positive MicroparticlesHilal Hekimoğlu0Selin Fulya Toprak1Selçuk Sözer2İstanbul University, Aziz Sancar Institute of Experimental Medicine, Department of Genetics, İstanbul, Turkey; Institute of Health Sciences, İstanbul University, İstanbul, Turkeyİstanbul University, Aziz Sancar Institute of Experimental Medicine, Department of Genetics, İstanbul, Turkey; Institute of Health Sciences, İstanbul University, İstanbul, Turkeyİstanbul University, Aziz Sancar Institute of Experimental Medicine, Department of Genetics, İstanbul, TurkeyObjective: Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) have a high propensity for thrombosis, which has been attributed to increased blood counts, endothelial cell (EC) dysfunction, and inflammation. The presence of the JAK2V617F mutation in the ECs of MPN patients has been confirmed, but the consequences of EC involvement by JAK2V617F in the pathogenesis of thrombosis are unclear. Endothelial microparticles (EMPs) released from ECs play an important role in endothelial dysfunction and also in the intercellular exchange of biological signals and information. Several studies have revealed that patients with JAK2V617F and a thrombosis history have increased numbers of MPs in their circulation. Materials and Methods: The current study utilized a lentiviral transduction model of JAK2 wild type (JAK2wt) or JAK2V617F encoding green fluorescent protein (GFP) into human umbilical vein ECs to determine the effect of JAK2V617F on ECs. EC infected with JAK2V617F, JAK2WT, and only-GFP were tested after two days of culture. Results: The proteins of ECs that potentially play a role in the development of thrombosis, including endothelial protein C receptor, thrombomodulin, and tissue factor, were detected by flow cytometry analysis with no statistical significance. Increased annexin-V uptake of JAK2V617F and JAK2wt ECs compared to GFP-alone ECs was detected. The EMP production in the supernatants of the EC culture was investigated. Genotyping of the EMPs revealed the presence of genomic DNA and RNA fragments in EMP cargos. JAK2V617F-positive DNA was detected in EMPs released from JAK2V617F-infected ECs and EMPs were shown to carry the genotype of the cell of origin. Conclusion: JAK2V617F-positive EMPs were shown for the first time in the literature. This novel research provides the first evidence that EMPs might regulate neighboring and distant cells via their cargo materials. Thus, the direct effect of JAK2V617F on ECs and their functions suggests that different mechanisms might play a role in the pathogenesis of thrombosis in MPNs.https://jag.journalagent.com/z4/download_fulltext.asp?pdir=tjh&un=TJH-57355jak2v617fendothelial cellsmicroparticlesextracellular genomic materials |
| spellingShingle | Hilal Hekimoğlu Selin Fulya Toprak Selçuk Sözer JAK2V617F-Positive Endothelial Cells Induce Apoptosis and Release JAK2V617F-Positive Microparticles Turkish Journal of Hematology jak2v617f endothelial cells microparticles extracellular genomic materials |
| title | JAK2V617F-Positive Endothelial Cells Induce Apoptosis and Release JAK2V617F-Positive Microparticles |
| title_full | JAK2V617F-Positive Endothelial Cells Induce Apoptosis and Release JAK2V617F-Positive Microparticles |
| title_fullStr | JAK2V617F-Positive Endothelial Cells Induce Apoptosis and Release JAK2V617F-Positive Microparticles |
| title_full_unstemmed | JAK2V617F-Positive Endothelial Cells Induce Apoptosis and Release JAK2V617F-Positive Microparticles |
| title_short | JAK2V617F-Positive Endothelial Cells Induce Apoptosis and Release JAK2V617F-Positive Microparticles |
| title_sort | jak2v617f positive endothelial cells induce apoptosis and release jak2v617f positive microparticles |
| topic | jak2v617f endothelial cells microparticles extracellular genomic materials |
| url | https://jag.journalagent.com/z4/download_fulltext.asp?pdir=tjh&un=TJH-57355 |
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