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Thrombopoietic stimulating activity of rhTyrRS (Y341A)
- Source :
- Scientific Reports, Scientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
- Publication Year :
- 2017
- Publisher :
- Nature Publishing Group UK, 2017.
-
Abstract
- Tumor radiotherapy induces hematopoietic organ damage and reduces thrombocyte counts. Thrombocytopenia is a common disease. Some studies have shown that tRNA synthetase plays not only catalytic tRNA aminoacylation roles, but also functions similarly to cytokines. Recombinant human tyrosyl-tRNA synthetase with a mutated Y341A (rhTyrRS (Y341A)) promotes megakaryocyte migrate from bone marrow to peripheral blood. It would promote megakaryocytes in the lungs adhering to vascular endothelial cells and resulting in the platelet production. The purpose of this research was to investigate the efficacy of rhTyrRS (Y341A) as a therapy for thrombocytopenia and to explore its mechanism of action. We found platelet number was effectively increased by rhTyrRS (Y341A) via platelet count and reticulated platelets (RPs) flow cytometry. We also demonstrated radiation-induced thrombocytopenia could be prevented by rhTyrRS (Y341A). The results of immunohistochemistry and H&E staining showed the number of pulmonary mature megakaryocytes was significantly increased in rhTyrRS (Y341A) treated groups. In transgenic zebrafish larvae, confocal microscopy results showed rhTyrRS (Y341A) promoted the migration and adhesion of megakaryocytes. These results suggested that rhTyrRS (Y341A) promote megakaryocytes in bone marrow migrating to lungs through blood circulation. rhTyrRS (Y341A) may be an effective medicine which could be used to treat patients suffering from thrombocytopenia.
- Subjects :
- 0301 basic medicine
Male
lcsh:Medicine
Animals, Genetically Modified
Rats, Sprague-Dawley
Mice
Megakaryocyte
Cell Movement
Tyrosine-tRNA Ligase
Neoplasms
Platelet
lcsh:Science
Zebrafish
Multidisciplinary
medicine.diagnostic_test
Recombinant Proteins
medicine.anatomical_structure
Treatment Outcome
Immunohistochemistry
Female
medicine.symptom
Megakaryocytes
Blood Platelets
Biology
Article
Flow cytometry
Thrombopoiesis
03 medical and health sciences
medicine
Human Umbilical Vein Endothelial Cells
TRNA aminoacylation
Animals
Humans
030102 biochemistry & molecular biology
Radiotherapy
Platelet Count
lcsh:R
biology.organism_classification
Thrombocytopenia
Rats
Mice, Inbred C57BL
Disease Models, Animal
030104 developmental biology
Mechanism of action
Immunology
Mutation
Cancer research
lcsh:Q
Bone marrow
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....1d6f151cff94efd1e3e1a8c756a812ab