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rhTyrRS（Y341A）的促血小板生成活性。

Thrombopoietic stimulating activity of rhTyrRS (Y341A).

机构信息

The Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Fudan University, 238# P.O. Box, 138 Yixueyan Rd., Shanghai, 200032, Shanghai Shi, China.

The Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 238# P.O. Box, 138 Yixueyan Rd., Shanghai, 200032, Shanghai Shi, China.

出版信息

Sci Rep. 2017 Sep 22;7(1):12184. doi: 10.1038/s41598-017-12073-4.

DOI:10.1038/s41598-017-12073-4
PMID:28939876
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5610193/
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.

摘要

肿瘤放疗可导致造血器官损伤并减少血小板计数。血小板减少症是一种常见疾病。一些研究表明，tRNA 合成酶不仅具有催化 tRNA 氨酰化的作用，而且还具有类似细胞因子的功能。突变的 Y341A 重组人酪氨酸-tRNA 合成酶（rhTyrRS（Y341A））可促进巨核细胞从骨髓迁移到外周血。它会促进肺部的巨核细胞黏附血管内皮细胞，导致血小板生成。本研究旨在探讨 rhTyrRS（Y341A）作为治疗血小板减少症的疗效及其作用机制。我们发现 rhTyrRS（Y341A）可通过血小板计数和网织血小板（RPs）流式细胞术有效增加血小板数量。我们还证明 rhTyrRS（Y341A）可预防辐射诱导的血小板减少症。免疫组织化学和 H&E 染色结果表明，rhTyrRS（Y341A）处理组肺成熟巨核细胞数量明显增加。在转基因斑马鱼幼虫中，共聚焦显微镜结果表明 rhTyrRS（Y341A）促进了巨核细胞的迁移和黏附。这些结果表明 rhTyrRS（Y341A）通过血液循环促进骨髓中的巨核细胞向肺部迁移。rhTyrRS（Y341A）可能是一种有效的药物，可用于治疗血小板减少症患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fca5/5610193/fab0fe1d4dd0/41598_2017_12073_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fca5/5610193/ffa6ad29029f/41598_2017_12073_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fca5/5610193/f1d9d19d0a92/41598_2017_12073_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fca5/5610193/ca121c67966b/41598_2017_12073_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fca5/5610193/d3903b50c6c0/41598_2017_12073_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fca5/5610193/fab0fe1d4dd0/41598_2017_12073_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fca5/5610193/ffa6ad29029f/41598_2017_12073_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fca5/5610193/f1d9d19d0a92/41598_2017_12073_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fca5/5610193/ca121c67966b/41598_2017_12073_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fca5/5610193/d3903b50c6c0/41598_2017_12073_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fca5/5610193/fab0fe1d4dd0/41598_2017_12073_Fig5_HTML.jpg

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本文引用的文献

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The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors.肺是血小板生物发生的场所，也是造血祖细胞的储存库。
Nature. 2017 Apr 6;544(7648):105-109. doi: 10.1038/nature21706. Epub 2017 Mar 22.
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Drug discovery: Zebrafish uncover novel antipsychotics.药物发现：斑马鱼揭示新型抗精神病药物
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