Overexpression of COMP-Angiopoietin-1 in K14-Expressing Cells Impairs Hematopoiesis and Disturbs Erythrocyte Maturation
| Autor: | Sung-Ho Kook, Han-Sol So, Hyun-Jaung Sim, Jeong-Chae Lee, Sher Bahadur Poudel, Govinda Bhattarai, Eui-Sic Cho, Min-Hye Kim, Jae-Won Hwang |
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| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
Myeloid Stromal cell Mesenchymal stem cell Cell Biology General Medicine Biology Cell biology 03 medical and health sciences Haematopoiesis 0302 clinical medicine medicine.anatomical_structure Erythrocyte maturation medicine Erythropoiesis Bone marrow Stem cell Molecular Biology 030217 neurology & neurosurgery 030304 developmental biology |
| Zdroj: | Molecules and Cells. 44:254-266 |
| ISSN: | 0219-1032 |
| Popis: | Numerous studies highlight the potential benefits potentials of supplemental cartilage oligomeric matrix protein-angiopoietin-1 (COMP-Ang1) through improved angiogenic effects. However, our recent findings show that excessive overexpression of COMP-Ang1 induces an impaired bone marrow (BM) microenvironment and senescence of hematopoietic stem cells (HSCs). Here, we investigated the underlying mechanisms of how excessive COMP-Ang1 affects the function of BM-conserved stem cells and hematopoiesis using K14-Cre;inducible-COMP-Ang1-transgenic mice. Excessive COMP-Ang1 induced peripheral egression and senescence of BM HSCs and mesenchymal stem cells (MSCs). Excessive COMP-Ang1 also caused abnormal hematopoiesis along with skewed differentiation of HSCs toward myeloid lineage rather than lymphoid lineage. Especially, excessive COMP-Ang1 disturbed late-stage erythroblast maturation, followed by decreased expression of stromal cell-derived factor 1 (SDF-1) and globin transcription factor 1 (GATA-1) and increased levels of superoxide anion and p-p38 kinase. However, transplantation with the mutant-derived BM cells or treatment with rhCOMP-Ang1 protein did not alter the frequency or GATA-1 expression of erythroblasts in recipient mice or in cultured BM cells. Together, our findings suggest that excessive COMP-Ang1 impairs the functions of BM HSCs and MSCs and hematopoietic processes, eventually leading to abnormal erythropoiesis via imbalanced SDF-1/CXCR4 axis and GATA-1 expression rather than Ang1/Tie2 signaling axis alterations. |
| Databáze: | OpenAIRE |
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