Iron Overload Impairs Bone Marrow Mesenchymal Stromal Cells from Higher-Risk MDS Patients by Regulating the ROS-Related Wnt/β-Catenin Pathway
The bone marrow microenvironment plays important roles in the progression of the myelodysplastic syndrome (MDS). The higher incidence of ASXL1 and TET2 gene mutations in our iron overload (IO) MDS patients suggests that IO may be involved in the pathogenesis of MDS. The effects of IO damaging bone m...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2020/8855038 |
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| author | Lei Huang Zhaoyun Liu Hui Liu Kai Ding Fu Mi Chenhuan Xiang Guanrou Wang Yixuan Guo Rong Fu |
| author_facet | Lei Huang Zhaoyun Liu Hui Liu Kai Ding Fu Mi Chenhuan Xiang Guanrou Wang Yixuan Guo Rong Fu |
| author_sort | Lei Huang |
| collection | DOAJ |
| description | The bone marrow microenvironment plays important roles in the progression of the myelodysplastic syndrome (MDS). The higher incidence of ASXL1 and TET2 gene mutations in our iron overload (IO) MDS patients suggests that IO may be involved in the pathogenesis of MDS. The effects of IO damaging bone marrow mesenchymal stromal cells (MSCs) from higher-risk MDS patients were investigated. In our study, IO decreased the quantity and weakened the abilities of proliferation and differentiation of MSCs, and it inhibited the gene expressions of VEGFA, CXCL12, and TGF-β1 in MSCs regulating hematopoiesis. The increased level of reactive oxygen species (ROS) in MSCs caused by IO might be inducing apoptosis by activating caspase3 signals and involving in MDS progression by activating β-catenin signals. The damages of MSCs caused by IO could be partially reversed by an antioxidant or an iron chelator. Furthermore, the MSCs in IO MDS/AML patients had increased levels of ROS and apoptosis, and the expressions of caspase3 and β-catenin were increased even further. In conclusion, IO affects gene stability in higher-risk MDS patients and impairs MSCs by inducing ROS-related apoptosis and activating the Wnt/β-catenin signaling pathway, which could be partially reversed by an antioxidant or an iron chelator. |
| format | Article |
| id | doaj-art-27605749cc3c485ca6f0651caa718c55 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-27605749cc3c485ca6f0651caa718c552025-02-03T01:27:55ZengWileyStem Cells International1687-966X1687-96782020-01-01202010.1155/2020/88550388855038Iron Overload Impairs Bone Marrow Mesenchymal Stromal Cells from Higher-Risk MDS Patients by Regulating the ROS-Related Wnt/β-Catenin PathwayLei Huang0Zhaoyun Liu1Hui Liu2Kai Ding3Fu Mi4Chenhuan Xiang5Guanrou Wang6Yixuan Guo7Rong Fu8Department of Hematology, Tianjin Medical University General Hospital, Tianjin 300052, ChinaDepartment of Hematology, Tianjin Medical University General Hospital, Tianjin 300052, ChinaDepartment of Hematology, Tianjin Medical University General Hospital, Tianjin 300052, ChinaDepartment of Hematology, Tianjin Medical University General Hospital, Tianjin 300052, ChinaDepartment of Hematology, Tianjin Medical University General Hospital, Tianjin 300052, ChinaDepartment of Hematology, Tianjin Medical University General Hospital, Tianjin 300052, ChinaDepartment of Hematology, Tianjin Medical University General Hospital, Tianjin 300052, ChinaDepartment of Hematology, Tianjin Medical University General Hospital, Tianjin 300052, ChinaDepartment of Hematology, Tianjin Medical University General Hospital, Tianjin 300052, ChinaThe bone marrow microenvironment plays important roles in the progression of the myelodysplastic syndrome (MDS). The higher incidence of ASXL1 and TET2 gene mutations in our iron overload (IO) MDS patients suggests that IO may be involved in the pathogenesis of MDS. The effects of IO damaging bone marrow mesenchymal stromal cells (MSCs) from higher-risk MDS patients were investigated. In our study, IO decreased the quantity and weakened the abilities of proliferation and differentiation of MSCs, and it inhibited the gene expressions of VEGFA, CXCL12, and TGF-β1 in MSCs regulating hematopoiesis. The increased level of reactive oxygen species (ROS) in MSCs caused by IO might be inducing apoptosis by activating caspase3 signals and involving in MDS progression by activating β-catenin signals. The damages of MSCs caused by IO could be partially reversed by an antioxidant or an iron chelator. Furthermore, the MSCs in IO MDS/AML patients had increased levels of ROS and apoptosis, and the expressions of caspase3 and β-catenin were increased even further. In conclusion, IO affects gene stability in higher-risk MDS patients and impairs MSCs by inducing ROS-related apoptosis and activating the Wnt/β-catenin signaling pathway, which could be partially reversed by an antioxidant or an iron chelator.http://dx.doi.org/10.1155/2020/8855038 |
| spellingShingle | Lei Huang Zhaoyun Liu Hui Liu Kai Ding Fu Mi Chenhuan Xiang Guanrou Wang Yixuan Guo Rong Fu Iron Overload Impairs Bone Marrow Mesenchymal Stromal Cells from Higher-Risk MDS Patients by Regulating the ROS-Related Wnt/β-Catenin Pathway Stem Cells International |
| title | Iron Overload Impairs Bone Marrow Mesenchymal Stromal Cells from Higher-Risk MDS Patients by Regulating the ROS-Related Wnt/β-Catenin Pathway |
| title_full | Iron Overload Impairs Bone Marrow Mesenchymal Stromal Cells from Higher-Risk MDS Patients by Regulating the ROS-Related Wnt/β-Catenin Pathway |
| title_fullStr | Iron Overload Impairs Bone Marrow Mesenchymal Stromal Cells from Higher-Risk MDS Patients by Regulating the ROS-Related Wnt/β-Catenin Pathway |
| title_full_unstemmed | Iron Overload Impairs Bone Marrow Mesenchymal Stromal Cells from Higher-Risk MDS Patients by Regulating the ROS-Related Wnt/β-Catenin Pathway |
| title_short | Iron Overload Impairs Bone Marrow Mesenchymal Stromal Cells from Higher-Risk MDS Patients by Regulating the ROS-Related Wnt/β-Catenin Pathway |
| title_sort | iron overload impairs bone marrow mesenchymal stromal cells from higher risk mds patients by regulating the ros related wnt β catenin pathway |
| url | http://dx.doi.org/10.1155/2020/8855038 |
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