Insulin-like growth factor-1 fused with thrombopoietin mimetic peptide effectively increase platelets count in vivo

被引:0
作者
Zhang, Hai-Tao [1 ,2 ]
Li, Zheng-Wu [2 ]
Guo, Chang-Hong [1 ]
Zhang, Xiu-Qin [2 ]
Chen, Yu-Jun
Li, Hui-Cheng [2 ]
机构
[1] Harbin Normal Univ, Coll Life Sci & Technol, Key Lab Mol Cytogenet & Genet Breeding Heilongjia, Harbin 150025, Peoples R China
[2] Harbin Pharmaceut Grp, Ctr Res & Dev, Harbin, Peoples R China
关键词
PHARMACOKINETICS; EXPRESSION; PROTEINS;
D O I
暂无
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objectives: To design the expression of fusion proteins containing one or 2 thrombopoietin mimetic peptide (TMP). Methods: This study was conducted at Harbin Pharmaceutical Group Research and Development Center, Harbin, China from June 2009 to January 2010. We designed the protein that was fused to the C-terminus of insulin-like growth factors (IGF-1) by a flexible peptide linker by Dami cell proliferation assay, colony-forming assay, and analysis of platelet in mice to prove our hypothesis. The total number of mice used was 48 in all 4 groups. Results: The fusion proteins were produced in Escherichia coli BL21 (DE3) at up to 26% of the total cell proteins. Subsequent biological activity assays showed that the fusion proteins exhibited higher potency than recombinant human thrombopoietin (TPO). Our results showed that the fusion proteins IGF-1-TMP exhibited higher biological activities than TMP in Dami cell proliferation, human cord blood cell colony-forming assays, and in experiments on acute myeloid radiation sickness mice, which can effectively increase the number of platelets. Conclusion: Experiments in mice and biology activity assay, which can effectively increase the number of platelets, indicated that it has a potential role in pharmaceutical applications for the treatment of thrombocytopenia.
引用
收藏
页码:254 / 259
页数:6
相关论文
共 17 条
[1]   Expression of insulin-like growth factors IGF-I and IGF-II, and their receptors during the growth and megakaryocytic differentiation of K562 cells [J].
Aro, ALA ;
Savikko, J ;
Pulkkinen, V ;
von Willebrand, E .
LEUKEMIA RESEARCH, 2002, 26 (09) :831-837
[2]   The fusion protein MEN 11301 (granulocyte-macrophage colony stimulating factor/erythropoietin) acts as a potent inducer of erythropoiesis [J].
Battaglia, A ;
Fattorossi, A ;
Pierelli, L ;
Bonanno, G ;
Marone, M ;
Ranelletti, FO ;
Coscarella, A ;
De Santis, R ;
Bach, S ;
Mancuso, S ;
Scambia, G .
EXPERIMENTAL HEMATOLOGY, 2000, 28 (05) :490-498
[3]   Immunogenicity of thrombopoietin mimetic peptide GW395058 in BALB/c mice and New Zealand white rabbits: Evaluation of the potential for thrombopoietin neutralizing antibody production in man [J].
de Serres, M ;
Ellis, B ;
Dillberger, JE ;
Rudolph, SK ;
Hutchins, JT ;
Boytos, CM ;
Weigl, DL ;
DePrince, RB .
STEM CELLS, 1999, 17 (04) :203-209
[4]   Thrombopoietin: a pan-hematopoietic cytokine [J].
Geddis, AE ;
Linden, HM ;
Kaushansky, K .
CYTOKINE & GROWTH FACTOR REVIEWS, 2002, 13 (01) :61-73
[5]   Bi-functional cytokine fusion proteins for gene therapy and antibody-targeted treatment of cancer [J].
Gillies, SD ;
Lan, Y ;
Brunkhorst, B ;
Wong, WK ;
Li, Y ;
Lo, KM .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2002, 51 (08) :449-460
[6]   Chromatographic methods for the isolation of and refolding of proteins from, Escherichia coli inclusion bodies [J].
Gu, ZY ;
Weidenhaupt, M ;
Ivanova, N ;
Pavlov, M ;
Xu, BZ ;
Su, ZG ;
Janson, JC .
PROTEIN EXPRESSION AND PURIFICATION, 2002, 25 (01) :174-179
[7]   Insulin-like growth factor-1 potentiates platelet activation via the IRS/PI3Kα pathway [J].
Hers, Ingeborg .
BLOOD, 2007, 110 (13) :4243-4252
[8]   Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis [J].
Klusmann, Jan-Henning ;
Godinho, Frank J. ;
Heitmann, Kirsten ;
Maroz, Aliaksandra ;
Koch, Mia Lee ;
Reinhardt, Dirk ;
Orkin, Stuart H. ;
Li, Zhe .
GENES & DEVELOPMENT, 2010, 24 (15) :1659-1672
[9]   Plasminogen activator inhibitor-1 fused with erythropoietin (EPO) mimetic peptide (EMP) enhances the EPO activity of EMP [J].
Kuai, LT ;
Wu, CL ;
Qiu, QF ;
Zhang, J ;
Zhou, AW ;
Wang, SQ ;
Zhang, HY ;
Song, Q ;
Liao, SN ;
Han, Y ;
Liu, JN ;
Ma, Z .
JOURNAL OF PEPTIDE RESEARCH, 2000, 56 (02) :59-62
[10]   Thrombopoietin and Thrombopoietin Mimetics in the Treatment of Thrombocytopenia [J].
Kuter, David J. .
ANNUAL REVIEW OF MEDICINE, 2009, 60 :193-206