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ZFIN ID: ZDB-PUB-170924-4
Thrombopoietic stimulating activity of rhTyrRS (Y341A)
Jinchao, Y., Yanling, Z., Xu, W., Bing, Z., Yuhao, Y., Weiran, Z., Shaoyang, S., Liyun, M., Yun, S., Ling, Z., Min, Y., Wei, M.
Date: 2017
Source: Scientific Reports   7: 12184 (Journal)
Registered Authors:
Keywords: Cell migration, Drug discovery
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Blood Platelets/drug effects*
  • Blood Platelets/radiation effects
  • Cell Movement/drug effects
  • Disease Models, Animal
  • Female
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Male
  • Megakaryocytes/drug effects
  • Megakaryocytes/radiation effects
  • Mice
  • Mice, Inbred C57BL
  • Mutation
  • Neoplasms/radiotherapy
  • Platelet Count
  • Radiotherapy/adverse effects
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins/administration & dosage
  • Recombinant Proteins/genetics
  • Thrombocytopenia/drug therapy*
  • Thrombocytopenia/etiology
  • Thrombopoiesis/drug effects*
  • Thrombopoiesis/radiation effects
  • Treatment Outcome
  • Tyrosine-tRNA Ligase/administration & dosage*
  • Tyrosine-tRNA Ligase/genetics
  • Zebrafish
PubMed: 28939876 Full text @ Sci. Rep.
FIGURES
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.
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