P1002: Anti-fibrotic activity of BMP2 in bone marrow-derived mesenchymal stromal cells of myeloproliferative neoplasms
Аутори
Subotički, Tijana![](/themes/MirageRIMI/images/orcid.png)
Živković, Emilija
![](/themes/MirageRIMI/images/orcid.png)
Mitrović Ajtić, Olivera
![](/themes/MirageRIMI/images/orcid.png)
Vukotić, Milica
Đikić, Dragoslava
![](/themes/MirageRIMI/images/orcid.png)
Dragojević, Teodora
![](/themes/MirageRIMI/images/orcid.png)
Šefer, D.
Bižić, S.
Santibanez, Juan F.
![](/themes/MirageRIMI/images/orcid.png)
Gotić, M.
Čokić, Vladan P.
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Background: Myeloproliferative neoplasms (MPN) are clonal hematopoietic disorders that include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Bone marrow fibrosis (BMF) is a shared feature of all MPN, although it is most pronounced in PMF and represents a major diagnostic criteria. Studies suggest a correlation between the grade of BMF and prognosis of MPN, with more fibrosis associated with worse outcome. A large body of evidence has suggested that transforming growth factor beta (TGF-β) is among the most prominent inducers of fibrotic processes. Bone morphogenetic proteins (BMPs) are major regulators of cell fate in tissue homeostasis. In MPN, bone marrow-derived mesenchymal stromal cells (BM-MSC) are identified as a major cellular source of fibrosis, but exact molecular mechanism involved have not been identified so far. Aims: In addition to apoptosis and prolifration, we analyzed the effect of BMP2 and TGF- β / SMAD signaling pathway on th...e fibrotic phenotype of BM-MSC isolated from MPN patients and healthy donors. Methods: Bone marrow aspirates from 5 newly diagnosed MPN patients (3 PMF and 2 PV patients) and 3 healthy donors were analyzed by immunofluorescence expression of fibronectin and alpha smooth muscle Actin (αSMA), after treatment with TGF-β and / or BMP2. Using immunocytochemistry, we analyzed HEL 92.1.7 cells with a homozygous expression of JAK2V617F for proliferation (Ki67) and apoptosis (ssDNA) during exposure to BMP2 and selective BMP signaling inhibitor LDN-193189. Results: Our results showed that TGF-β significantly increased fibronectin expression, in contrast to BMP2, in BM-MSC of healthy donors. Also, the joint treatment of TGF-β and BMP2 reduced the level of fibronectin expression relative to TGF-β. In addition, TGF-β increased αSMA expression in BM-MSC from healthy donors. In contrast, BMP2 reduces the expression of αSMA and fibronectin in BM-MSC of healthy donors.BMP2 significantly reduced fibronectin expression in BM-MSC compared to untreated cells of patients with MPN. BMP2 dose dependently and significantly (p<0.01) increased the proliferation of HEL 92.1.7 cells, while the BMP signaling inhibitor LDN-193189 also demonstrated dose dependence in stimulation of proliferation (p<0.001). Apoptosis of HEL 92.1.7 cells was slightly affected by BMP2 and LDN-193189. Summary/Conclusion: Our results show that BMP2 has anti-fibrotic activity that is antagonistic to TGF-β. This indicate that BMP2 may modify the TGF-β signaling pathway.
Извор:
HemaSphere - EHA2022 Hybrid Congress Abstract Book, 2022, 6, Suppl (S3), 892-893Издавач:
- Wolters Kluwer Health, Inc.
Институција/група
Institut za medicinska istraživanjaTY - CONF AU - Subotički, Tijana AU - Živković, Emilija AU - Mitrović Ajtić, Olivera AU - Vukotić, Milica AU - Đikić, Dragoslava AU - Dragojević, Teodora AU - Šefer, D. AU - Bižić, S. AU - Santibanez, Juan F. AU - Gotić, M. AU - Čokić, Vladan P. PY - 2022 UR - http://rimi.imi.bg.ac.rs/handle/123456789/1490 AB - Background: Myeloproliferative neoplasms (MPN) are clonal hematopoietic disorders that include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Bone marrow fibrosis (BMF) is a shared feature of all MPN, although it is most pronounced in PMF and represents a major diagnostic criteria. Studies suggest a correlation between the grade of BMF and prognosis of MPN, with more fibrosis associated with worse outcome. A large body of evidence has suggested that transforming growth factor beta (TGF-β) is among the most prominent inducers of fibrotic processes. Bone morphogenetic proteins (BMPs) are major regulators of cell fate in tissue homeostasis. In MPN, bone marrow-derived mesenchymal stromal cells (BM-MSC) are identified as a major cellular source of fibrosis, but exact molecular mechanism involved have not been identified so far. Aims: In addition to apoptosis and prolifration, we analyzed the effect of BMP2 and TGF- β / SMAD signaling pathway on the fibrotic phenotype of BM-MSC isolated from MPN patients and healthy donors. Methods: Bone marrow aspirates from 5 newly diagnosed MPN patients (3 PMF and 2 PV patients) and 3 healthy donors were analyzed by immunofluorescence expression of fibronectin and alpha smooth muscle Actin (αSMA), after treatment with TGF-β and / or BMP2. Using immunocytochemistry, we analyzed HEL 92.1.7 cells with a homozygous expression of JAK2V617F for proliferation (Ki67) and apoptosis (ssDNA) during exposure to BMP2 and selective BMP signaling inhibitor LDN-193189. Results: Our results showed that TGF-β significantly increased fibronectin expression, in contrast to BMP2, in BM-MSC of healthy donors. Also, the joint treatment of TGF-β and BMP2 reduced the level of fibronectin expression relative to TGF-β. In addition, TGF-β increased αSMA expression in BM-MSC from healthy donors. In contrast, BMP2 reduces the expression of αSMA and fibronectin in BM-MSC of healthy donors.BMP2 significantly reduced fibronectin expression in BM-MSC compared to untreated cells of patients with MPN. BMP2 dose dependently and significantly (p<0.01) increased the proliferation of HEL 92.1.7 cells, while the BMP signaling inhibitor LDN-193189 also demonstrated dose dependence in stimulation of proliferation (p<0.001). Apoptosis of HEL 92.1.7 cells was slightly affected by BMP2 and LDN-193189. Summary/Conclusion: Our results show that BMP2 has anti-fibrotic activity that is antagonistic to TGF-β. This indicate that BMP2 may modify the TGF-β signaling pathway. PB - Wolters Kluwer Health, Inc. C3 - HemaSphere - EHA2022 Hybrid Congress Abstract Book T1 - P1002: Anti-fibrotic activity of BMP2 in bone marrow-derived mesenchymal stromal cells of myeloproliferative neoplasms EP - 893 IS - Suppl (S3) SP - 892 VL - 6 DO - 10.1097/01.HS9.0000846876.57509.68 ER -
@conference{ author = "Subotički, Tijana and Živković, Emilija and Mitrović Ajtić, Olivera and Vukotić, Milica and Đikić, Dragoslava and Dragojević, Teodora and Šefer, D. and Bižić, S. and Santibanez, Juan F. and Gotić, M. and Čokić, Vladan P.", year = "2022", abstract = "Background: Myeloproliferative neoplasms (MPN) are clonal hematopoietic disorders that include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Bone marrow fibrosis (BMF) is a shared feature of all MPN, although it is most pronounced in PMF and represents a major diagnostic criteria. Studies suggest a correlation between the grade of BMF and prognosis of MPN, with more fibrosis associated with worse outcome. A large body of evidence has suggested that transforming growth factor beta (TGF-β) is among the most prominent inducers of fibrotic processes. Bone morphogenetic proteins (BMPs) are major regulators of cell fate in tissue homeostasis. In MPN, bone marrow-derived mesenchymal stromal cells (BM-MSC) are identified as a major cellular source of fibrosis, but exact molecular mechanism involved have not been identified so far. Aims: In addition to apoptosis and prolifration, we analyzed the effect of BMP2 and TGF- β / SMAD signaling pathway on the fibrotic phenotype of BM-MSC isolated from MPN patients and healthy donors. Methods: Bone marrow aspirates from 5 newly diagnosed MPN patients (3 PMF and 2 PV patients) and 3 healthy donors were analyzed by immunofluorescence expression of fibronectin and alpha smooth muscle Actin (αSMA), after treatment with TGF-β and / or BMP2. Using immunocytochemistry, we analyzed HEL 92.1.7 cells with a homozygous expression of JAK2V617F for proliferation (Ki67) and apoptosis (ssDNA) during exposure to BMP2 and selective BMP signaling inhibitor LDN-193189. Results: Our results showed that TGF-β significantly increased fibronectin expression, in contrast to BMP2, in BM-MSC of healthy donors. Also, the joint treatment of TGF-β and BMP2 reduced the level of fibronectin expression relative to TGF-β. In addition, TGF-β increased αSMA expression in BM-MSC from healthy donors. In contrast, BMP2 reduces the expression of αSMA and fibronectin in BM-MSC of healthy donors.BMP2 significantly reduced fibronectin expression in BM-MSC compared to untreated cells of patients with MPN. BMP2 dose dependently and significantly (p<0.01) increased the proliferation of HEL 92.1.7 cells, while the BMP signaling inhibitor LDN-193189 also demonstrated dose dependence in stimulation of proliferation (p<0.001). Apoptosis of HEL 92.1.7 cells was slightly affected by BMP2 and LDN-193189. Summary/Conclusion: Our results show that BMP2 has anti-fibrotic activity that is antagonistic to TGF-β. This indicate that BMP2 may modify the TGF-β signaling pathway.", publisher = "Wolters Kluwer Health, Inc.", journal = "HemaSphere - EHA2022 Hybrid Congress Abstract Book", title = "P1002: Anti-fibrotic activity of BMP2 in bone marrow-derived mesenchymal stromal cells of myeloproliferative neoplasms", pages = "893-892", number = "Suppl (S3)", volume = "6", doi = "10.1097/01.HS9.0000846876.57509.68" }
Subotički, T., Živković, E., Mitrović Ajtić, O., Vukotić, M., Đikić, D., Dragojević, T., Šefer, D., Bižić, S., Santibanez, J. F., Gotić, M.,& Čokić, V. P.. (2022). P1002: Anti-fibrotic activity of BMP2 in bone marrow-derived mesenchymal stromal cells of myeloproliferative neoplasms. in HemaSphere - EHA2022 Hybrid Congress Abstract Book Wolters Kluwer Health, Inc.., 6(Suppl (S3)), 892-893. https://doi.org/10.1097/01.HS9.0000846876.57509.68
Subotički T, Živković E, Mitrović Ajtić O, Vukotić M, Đikić D, Dragojević T, Šefer D, Bižić S, Santibanez JF, Gotić M, Čokić VP. P1002: Anti-fibrotic activity of BMP2 in bone marrow-derived mesenchymal stromal cells of myeloproliferative neoplasms. in HemaSphere - EHA2022 Hybrid Congress Abstract Book. 2022;6(Suppl (S3)):892-893. doi:10.1097/01.HS9.0000846876.57509.68 .
Subotički, Tijana, Živković, Emilija, Mitrović Ajtić, Olivera, Vukotić, Milica, Đikić, Dragoslava, Dragojević, Teodora, Šefer, D., Bižić, S., Santibanez, Juan F., Gotić, M., Čokić, Vladan P., "P1002: Anti-fibrotic activity of BMP2 in bone marrow-derived mesenchymal stromal cells of myeloproliferative neoplasms" in HemaSphere - EHA2022 Hybrid Congress Abstract Book, 6, no. Suppl (S3) (2022):892-893, https://doi.org/10.1097/01.HS9.0000846876.57509.68 . .