人血小板生成素cDNA转导促进小鼠生长与胰岛素样生长因子相关

赵建增,陈立敏,梅英杰,张国荣,王晓平

中国生物化学与分子生物学报 ›› 2000, Vol. 16 ›› Issue (04) : 524-528.

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中国生物化学与分子生物学报 ›› 2000, Vol. 16 ›› Issue (04) : 524-528.
论文

人血小板生成素cDNA转导促进小鼠生长与胰岛素样生长因子相关

  • 赵建增,陈立敏,梅英杰,张国荣,王晓平
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Human Thrombopoietin cDNA Transfer Promotes Mice Growth Associated with an Insulin-like Growth Factor

  • ZHAO Jian\|zeng,CHEN Li\|min,MEI Ying\|jie,ZHANG Guo\|rong,WANG Xiao\|ping
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摘要

人血小板生成素 ( TPO)基因转导能刺激小鼠生长 .将编码人 TPO的真核表达质粒pc DNA3 h TPO、野生型 pc DNA3 或生理盐水注射小鼠后肢肌肉 ,称量小鼠的体重、器官重 .用半定量 ELISA检测 TPO转导小鼠血清中胰岛素样生长因子 ( IGF) - 、 和血小板源生长因子( PDGF)水平 .结果发现 ,TPO基因转导能促进小鼠的生长 .这种促生长作用与年龄和性别有关 ,但与动物的种系无关 .8~ 1 2周龄雌鼠在基因转导后 1周生长开始加快 .在第 1、2、3和 4周的升高幅度分别为 4.3%、5.3%、4.1 %和 4.38% ( P分别 <0 .0 0 5、0 .0 0 2、0 .0 1和 0 .0 1 ) .小于 4周龄的幼鼠、大于 1 6周的老龄鼠 ,以及雄性鼠在基因转导后体重无明显改变 .半定量 ELISA分析发现 ,体重增加的成年雌性鼠 ,其血清中 IGFs和 PDGF均升高 .基因转导鼠血液中葡萄糖、甘油三酯及碱性磷酸酶水平升高 .结果表明 ,一些生长因子 ,特别是 IGF- ,介导着 TPO对转基因动物的生长刺激作用 .

Abstract

To study the effect of thrombopoietin(TPO) gene delivery on the growth of mice,human TPO plasmid DNA encapsulated with lipofectin was injected into mouse muscle.And female mice of 8-12 weeks old were found to have a significent body weight gain compared with the controls following the 1st,2nd,3rd and 4th week( P <0 005,0 002,0 01 and 0 01 respectively),which had a characteristic of rapid growth ( P <0 01) in liver and spleen.However,the change of body weight in such mice injected with TPO cDNA as the males of the same age,the young ones of less than 4 weeks or the females of more than 16 weeks were not significantly different.Semi\|quantitative ELISA analysis demonstrated that the serum levels of platelet derived growth factor(PDGF),insulin\|like growth factors(IGF\|)Ⅰ and Ⅱ in the delivered mice rose correspondingly.Serum glucose,triglyceride,and alkaline phosphatase were also increased.It is suggested that some other growth factors,especially IGF\|1,mediate part of in vivo activities of TPO.

关键词

血小板生成素 / 促生长 / 胰岛素样生长因子 / 血小板源性生长因子

Key words

Thrombopoietin / Growth\|promotion / IGF\|Ⅰ / IGF Ⅱ / PDGF

引用本文

导出引用
赵建增,陈立敏,梅英杰,张国荣,王晓平. 人血小板生成素cDNA转导促进小鼠生长与胰岛素样生长因子相关[J]. 中国生物化学与分子生物学报, 2000, 16(04): 524-528
ZHAO Jian\|zeng,CHEN Li\|min,MEI Ying\|jie,ZHANG Guo\|rong,WANG Xiao\|ping. Human Thrombopoietin cDNA Transfer Promotes Mice Growth Associated with an Insulin-like Growth Factor[J]. Chinese Journal of Biochemistry and Molecular Biology, 2000, 16(04): 524-528

参考文献

1  de Sauvage F J,Hass P E,Spencer S D,Malloy B E,Gurney AL ,Spencer S A,Darbonne W C,Henzel W J,Wong S C,KuangW J,Oles K J,Hultgren B,Solberg L A Jr,Goeddel D V,EatonD L .Stimulation of megakaryocytopoiesis and thrombopoiesisby the c-Mpl ligand.N ature,1994,3 69:5 3 3~ 5 3 8 2  Lok S,Kaushansky K,Holly R D,Kujiper JL ,Lofton-Day C E,Oort P J,Grant F J,Helpel M D,Burkhead S K,Kramer JM,Bell L A,Sprecher C A,Blumberg H,Johnson R,Prunkard D,Ching A F T,Mathewes S L,Balley M C,Forstrom JW,BuddleM M,Osborn S G,Evans S J,Sheppard P O,Presnell S R,O′Hara P J,Hagen F S,Roth G J,Foster D C.Cloning andexpression of the murine thrombopoietin c DNA and stim ulationof platelet production in vivo.N ature,1994,3 69:5 65~ 5 68 3  Yan X Q,L acey D,F letcher F,Hartley C,Mc Elroy P,Sun Y,Xia M,Mu S,Saris C,Hill D,Hawley R G,Mc Niece I K.Chronic exposure to retroviral vector encoded MGDF ( m pl-ligand) induces lineage-specific growth and differentiation ofmegakaryocytes in mice.Blood,1995 ,86:40 2 5~ 40 3 3 4  Ozaki S,Kosaka M,Ozaki K,Wakatsuki S,Hashimoto T,Miyazaki H. Thrombopoietin-responsible essentialthrom bocythaemia with myelofibrosis.Br J H aematol,1997,97:449~ 45 2 5  Wakikawa T,Shioi A,Hino M,Inaba M,Nishizawa Y,TatsumiN,Morii H,Otani S.Thrombopoietin inhibits in vitroosteoclastogenesis from murine bone marrow cells.Endocrinology,1997,13 8:4160~ 4166 6  Kubota Y,Kashima M,Koishi M,Kawa Y,Mizoguchi M.Effects of thrombopoietin on the proliferation and cell adhesionmolecule expression of hum an endothelial cells( abstract) .ExpH ematol,1996,2 4:10 69 7  Fujimoto T,Katsutani S,Fujii T,Kimura A,Miyazaki H,Fujimura K.Thrombopoietin induces the expression of one ofthe interferon-inducible gene fam ily,9-2 7:an analysis of thethrombopoietin action ( abstract) .Blood,1996,88( 10 suppl.1) :63 a 8  Bobik R,Hong Y,Breier G,Martin J F,Erusalimsky J D.Thrombopoietin stimulates VEGF release from c-Mpl-expressing cell lines and haematopoietic progenitors.F EBSL ett,1998,42 3 :10~ 14 9  Cardier J E,Dempsey J.Thrombopoietin and its receptor,c-mpl,are constitutively expressed by m ouse liver endothelialcells:evidence of thrombopoietin as a growth factor for liverendothelial cells.Blood,1998,91:92 3~ 92 9 10  Mitjavila M T,Filippi M D,Cohen-Solal K,L e Pesteur F,Vainchenker W,Sainteny F.The Mpl-ligand is involved in thegrowth-promoting activity of the murine stromal cell line MS-5on ES cell-derived hematopoiesis.Exp H ematol,1998,2 6:12 4~ 13 4 11 赵建增 ,刘丽 ,陈惠仁 ,梅英杰 .血小板生成素基因在体内的表达及对造血祖细胞增殖活性的影响 .中国生物化学与分子生物学报 ( Zhao JZ,L iu L ,Chen H R,Mei Y J.Expression of humanthrom bopoietin c DNA in mice and the effects on proliferation ofhematopoietic progenitor cells.Chin J Biochem Mol Biol) ,1998,14 ( 2 ) :117~ 12 1 12 赵建增 ,刘丽 ,梅英杰 .外源血小板生成素基因体内导入对循环免疫因子水平的影响 .中国免疫学杂志 ( Zhao JZ,L iu L,Mei YJ.Effects of thrombopoietin gene delivery on the concentrationof serum cytokines in m ice.Chin J Immunol) 1999,15 :10 3~ 10 5 13  Jansen M,van Schaik F M A,Ricker A T,Bullock B,Woods DE,Gabbay K H,Nussbaum A L,Sussenbach,Van den Brande JL .Sequence of c DNA encoding human insulin-like growthfactor precursor.N ature,1983 ,3 0 6:60 9~ 611 14  Stempien M M,Fong N F ,Ball L B,Bell G I.Sequence of aplacental c DNA encoding the mouse insulin-like growth factor precursor.DN A,1986,5 :3 5 7~ 3 61 15  Palmiter R D,Brinster R L ,Hammer R E,Trumbauer M E,Rosenfeld M G,Birnberg N C,Evans R M.Dram atic growth ofmice that develop from eggs microinjected withmetallothionein-growth hormone fusion genes.N ature,1982 ,3 0 0 :611~ 615 16  Palmiter R D,Norstedt G,Gelinas R E,Hammer R E,BrinsterR L.Metallothionein-human GH fusion genes stimulate growthof mice.Science,1983 ,2 2 2 :80 9~ 814 17 Mathews L S,Hammer R E,Behringer R R,D' ercole A J,Bell GI,Brinster R L ,Palmiter R A. Growth enhancement oftransgenic mice expression human insulin-like growth factor .Endocrinology,1988,12 3 :2 82 7~ 2 83 3 18  Kooijman R,Willems M,Rijkers G T,Brinkman A,van BuulOffers S C,Heijnen C J,Zegers B JM.Effects of insulin-likegrowth factors and growth horm one on the in vitro proliferationof T lymphocytes.J N euroimmunol,1992 ,3 8:95~ 10 4 19  Kooijman R,van Buul-Offers S C,Scholtens L E,Schuurman HJ,Van den Brande L J,Zegers B J M.T cell development ininsulin-like growth factor- transgenic mice.J Immunol,1995 ,15 4:5 73 6~ 5 745 2 0  Clark R,Strasser J Mc Cabe S,Robbins K,Jardieu P.Insulin-like growth factor-1stimulation of lymphopoiesis.J ClinInvest,1993 ,92 :5 40~ 5 48 2 1 赵建增 ,郭子宽 ,梅英杰 .血小板生成素基因转导鼠 T淋巴细胞的增殖和分化 .免疫学杂志 ( Zhao J Z,Guo Z K,Mei Y J.Thrombopoietin c DNA transfer promotes the proliferation anddifferentiation of T lymphocytes in mice.J Immunol) 1999,15 :3 2~ 3 4
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