Murine tribbles homolog 2 deficiency affects erythroid progenitor development and confers macrocytic anemia on mice
| Autor: | Chung-Leung Li, Huang-Wei Lien, Kou-Ray Lin, Hsin-Fang Yang-Yen, Liang-In Lin, Jeffrey J.Y. Yen, Chang-Jen Huang, Wei-Hao Liao |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Myeloid Protein Serine-Threonine Kinases Biology Hemolysis Article Mice 03 medical and health sciences Megakaryocyte Erythrocyte differentiation medicine Animals Humans Erythropoiesis Anemia Macrocytic Zebrafish Erythroid Precursor Cells Mice Knockout Multidisciplinary Intracellular Signaling Peptides and Proteins Cell biology 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Calcium-Calmodulin-Dependent Protein Kinases Immunology Tribbles Homolog 2 Ectopic expression Bone marrow |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Tribbles homolog 2 (Trib2) is a member of Tribbles protein pseudokinases and involves in apoptosis, autoimmunity, cancer, leukemia and erythropoiesis, however, the physiological function of Trib2 in hematopoietic system remains to be elucidated. Here, we report that Trib2 knockout (KO) mice manifest macrocytic anemia and increase of T lymphocytes. Although Trib2 deficient RBCs have similar half-life as the control RBCs, Trib2 KO mice are highly vulnerable to oxidant-induced hemolysis. Endogenous Trib2 mRNA is expressed in early hematopoietic progenitors, erythroid precursors and lymphoid lineages, but not in mature RBCs, myeloid progenitors and granulocytes. Consistently, flow cytometric analysis and in vitro colony forming assay revealed that deletion of Trib2 mainly affected erythroid lineage development and had no effect on either granulocyte or megakaryocyte lineages in bone marrow. Furthermore, a genetic approach using double knockout of Trib2 and C/ebpα genes in mice suggested that Trib2 promotes erythropoiesis independent of C/ebpα proteins in vivo. Finally, ectopic expression of human Trib2 in zebrafish embryos resulted in increased expression of erythropoiesis-related genes and of hemoglobin. Taking all data together, our results suggest that Trib2 positively promotes early erythrocyte differentiation and is essential for tolerance to hemolysis. |
| Databáze: | OpenAIRE |
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