title: Recombinant human tyrosyl-tRNA synthetase, a novel thrombopoietic agent.
abstract: Chemo- and radiotherapy induced thrombocytopenia present significant limitations for tumor therapy. In this study, we examined the therapeutic effect of recombinant human tyrosyl-tRNA synthetase (rhTyrRS) against development of thrombocytopenia in cyclophosphamide (CTX) treated mice. Our data indicate that intraperitoneal administration of at least 10 μg/day rhTyrRS for 7 days significantly prevents the decrease in platelets 8 days after CTX injection. The data further demonstrate that rhTyrRS promotes migration and aggregation of megakaryocytes to the bone marrow niche. Real-time PCR and flow cytometry reveal that VCAM-1 is particularly important for the adhesion. Together, these data suggest that rhTyrRS might be a useful therapeutic agent for chemotherapy-induced thrombocytopenia.
authors.affiliation: The Key Laboratory of Molecular Medicine, Ministry of Education, Fudan University, China; The Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, China.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Ling
authors.affiliation: The Key Laboratory of Molecular Medicine, Ministry of Education, Fudan University, China; The Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Yanling
authors.affiliation: The Key Laboratory of Molecular Medicine, Ministry of Education, Fudan University, China; The Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhe
authors.affiliation: The Key Laboratory of Molecular Medicine, Ministry of Education, Fudan University, China; The Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Kui
authors.affiliation: The Key Laboratory of Molecular Medicine, Ministry of Education, Fudan University, China; The Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Xiushi
authors.affiliation: The Key Laboratory of Molecular Medicine, Ministry of Education, Fudan University, China; The Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, China. Electronic address: minyu@shmu.edu.cn.
authors.forename: Yu
authors.initials: Y
authors.lastname: Min
authors.affiliation: The Key Laboratory of Molecular Medicine, Ministry of Education, Fudan University, China; The Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, China. Electronic address: weimo1025@shmu.edu.cn.
authors.forename: Mo
authors.initials: M
authors.lastname: Wei
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003520:Cyclophosphamide / Q000009:adverse effects; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008533:Megakaryocytes / Q000187:drug effects / Q000473:pathology; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology*; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D034061:Thrombopoiesis / Q000187:drug effects*; D014448:Tyrosine-tRNA Ligase / Q000494:pharmacology*
chemical_list: D011994:Recombinant Proteins; D003520:Cyclophosphamide; D014448:Tyrosine-tRNA Ligase
keywords: Aggregation of megakaryocytes; Cyclophosphamide; Cyclophosphamide (PubChem CID: 1001065998); Recombinant human tyrosyl tRNA synthetase; Thrombocytopenia; Vascular cell adhesion molecule