• 上海交通大學(xué)醫(yī)學(xué)院附屬新華醫(yī)院呼吸內(nèi)科( 上海 200092)通訊作者: 郭雪君, E-mail: guoxjz@ yahoo. com. cn#目前工作單位: 上海交通大學(xué)醫(yī)學(xué)院附屬第三人民醫(yī)院呼吸內(nèi)科;

目的  研究支氣管哮喘模型小鼠肺組織及肺T 細(xì)胞中三種β1, 3-N-乙酰糖基轉(zhuǎn)移酶( Fringe) RFNG、LFNG、MFNG 的基因和蛋白表達(dá)的特點(diǎn), 探討Fringe 是否與哮喘發(fā)病有關(guān)。方法  使用卵白蛋白腹腔注射后霧化吸入法制備BALB/ c 小鼠哮喘模型, 并設(shè)置生理鹽水對(duì)照組。經(jīng)Perco1 及尼龍毛法分離獲取肺T 細(xì)胞。采用半定量RT-PCR 檢測(cè)兩組小鼠肺組織及肺T 細(xì)胞中RFNG、LFNG、MFNG mRNA 表達(dá);Western blot 檢測(cè)兩組小鼠肺組織中RFNG、LFNG、MFNG 蛋白表達(dá)。結(jié)果  兩組小鼠肺組織及肺T 細(xì)胞中均存在三種Fringe 表達(dá)。哮喘組肺組織及肺T 細(xì)胞的RFNGmRNA 表達(dá)較對(duì)照組增加( 肺組織: 0. 92 ±0. 35 比0. 51 ±0. 13, P lt;0. 01; 肺T 細(xì)胞: 0. 33 ±0. 06 比0. 18 ±0. 07, P lt; 0. 01) ; LFNG mRNA 表達(dá)較對(duì)照組減少( 肺組織: 0. 77 ±0. 32 比1. 61 ±0. 31, P lt;0. 01; 肺T細(xì)胞: 0. 49 ±0. 19 比0. 71 ±0. 03, P  lt;0. 01) 。MFNG 在肺組織中的表達(dá)無(wú)明顯差異( 肺組織: 1. 44 ±0. 29 比1. 70 ±0. 44, P  gt; 0. 05) , 但MFNG 在肺T 細(xì)胞中的表達(dá)明顯減少( 0. 11 ±0. 03 比0. 52 ±0. 18, P  lt; 0. 01) 。肺組織中三種Fringe 蛋白表達(dá)與肺組織的mRNA 結(jié)果相似。哮喘組的RFNG 蛋白表達(dá)高于對(duì)照組( 1. 17 ±0. 04 比0. 68 ±0. 07, P  lt; 0. 05) , MFNG 蛋白表達(dá)在兩者之間沒有明顯的差異( 8. 10 ±0. 60 比9. 12 ±0. 07, P  gt; 0. 05) , 而LFNG 的蛋白表達(dá)則低于對(duì)照組( 4. 11 ±0. 38比6. 41 ±0. 11, P  lt;0. 05) 。結(jié)論  三種Fringe 的異常表達(dá)可能與支氣管哮喘的發(fā)病有關(guān)。

引用本文： 張杰,郭雪君. 哮喘小鼠肺組織和肺T 細(xì)胞β1, 3-N-乙酰糖基轉(zhuǎn)移酶的表達(dá). 中國(guó)呼吸與危重監(jiān)護(hù)雜志, 2010, 9(2): 128-132. doi: 復(fù)制

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1. Guo XJ,Zhou M,Ren LP,et al.Small interfering RNA mediated knockdown of Notch1 in lung T cells of asthmatic mouse affects T cells differentiation.Chin Med J 2009,122:2647-2651.
2. Gerard FH.Notch signaling in the immune system.J Leukoc Biol,2003,74:971-981.
3. Okajima T,Xu A,Irvine KD.Modulation of Notch-Ligand Binding by Protein O-Fucosyltransferase 1 and Fringe.J Biol Chem,2003;278:42340-42345.
4. Moloney DJ,Shair LH,Lu FM,et al.Mammalian Notch1 Is Modified with Two Unusual Forms of O-Linked Glycosylation Found on Epidermal Growth Factor-like Modules.J Biol Chem,2000,275:9604-9611.
5. Lei L,Xu A,Panin VM,et al.An O-fucose site in the ligand binding domain inhibits Notch activation,2003,130:6411-6421.
6. Xu A,Haines N,Dlugosz M.In Vitro Reconstitution of the Modulation of Drosophila Notch-Ligand Binding by Fringe.J Biol Chem,2007,282:35153-35162.
7. Yang LT,Nichols JT,Yao C,et al.Fringe Glycosyltransferases Differentially Modulate Notch1 Proteolysis Induced by Delta1 and Jagged1.Mol Biol Cell,2005,16:927-942.
8. 劉春濤,王曾禮,馮玉麟,等.哮喘動(dòng)物模型氣道中白細(xì)胞介素5和10的動(dòng)態(tài)變化及其意義.中華結(jié)核與呼吸雜志,2000;23:239-242.
9. 周敏,郭雪君,楊敏.支氣管哮喘BALB/c小鼠肺組織及肺T細(xì)胞中Notch1的表達(dá).上海交通大學(xué)學(xué)報(bào)（醫(yī)學(xué)版）,2007,27:161-164.
10. 楊敏,郭雪君,徐衛(wèi)國(guó)等.Notch配體在哮喘小鼠肺中的表達(dá).中國(guó)呼吸與危重監(jiān)護(hù)雜志,2007;6:257-230.
11. O′Byrne PM.Cytokines or Their Antagonists for the Treatment of Asthma.Chest,2006,130:244-250.
12. Pernis AB,Rothman PB.JAK-STAT signaling in asthma.J Clin Invest.2002,109:1279-1283.
13. Kheradmand F,Kiss A,Xu J,et al.A Protease-Activated Pathway Underlying Th Cell Type 2 Activation and Allergic Lung Disease1.J Immunol,2002,169:5904-5911.
14. Georas SN,Guo J,De Fanis U,et al.T-helper cell type-2 regulation in allergic disease.Eur Respir J,2005,26:1119-1137.
15. Gerard F.Hoyne Notch signaling in the immune system J.Leukoc.Biol.,Dec 2003,74:971.
16. Sun-Ok Yoon,Xin Zhang,Paul Berner,Bianca Blom,et al.Notch Ligands Expressed by Follicular Dendritic Cells Protect Germinal Center B Cells from Apoptosis J.Immunol.,Jul 2009,183:352 - 358.
17. Jonathon F.Hutton,Tessa Gargett,Timothy J.Sadlon,et al.Development of CD4+CD25+FoxP3+ regulatory T cells from cord blood hematopoietic progenitor cells J.Leukoc.Biol.,Mar 2009,85:445 - 451.
18. Amsen D,Blander JM,Lee G,et a1.Instruction of Distinct CD4 T Helper Cell Fates by Different Notch Ligands on Antigen-Presenting Cells.Cell,2004,ll7:515-526.
19. Amsen D,Antov A,Jankovic D,et al.Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch.Immunity,Jul 2007；27（1）:89-99.
20. Hozumi K,Abe N,Chiba S,et a1.Active form of notch member can enforce T lymphopoiesis on lymphoid progenitors in the monolayer culture specific for B cell development.J Immunol,2003,170:4973-4979.
21. Maekawa Y,Tsukumo S,Chiba H,et a1.Delta1-Notch3 Interactions Bias the Functional Differentiation of Activated CD4+ T Cells.Immunity,2003,19:549-559.
22. Shi S,Stanley P.Protein O-fucosyltransferase 1 is an essential component of Notch signaling pathways.PNAS.2003,100:5234-5239.
23. Okajima T,Irvine KD.Regulation of Notch Signaling by O-Linked Fucose.Cell,2002,111:893-904.
24. Ge CH,Stanley P.The O-fucose glycan in the ligand-binding domain of Notch1 regulates embryogenesis and T cell development.PNAS,2008,105:1539-1544.
25. Liangtung Y,James TN,Christine Y,et a1.Fringe Glycosyltransferases Differentially Modulate Notch1 Proteolysis Induced by Delta1 and Jagged1.Mol Biol Cell,2005,16:927-942.
  1. 1. Guo XJ,Zhou M,Ren LP,et al.Small interfering RNA mediated knockdown of Notch1 in lung T cells of asthmatic mouse affects T cells differentiation.Chin Med J 2009,122:2647-2651.
  2. 2. Gerard FH.Notch signaling in the immune system.J Leukoc Biol,2003,74:971-981.
  3. 3. Okajima T,Xu A,Irvine KD.Modulation of Notch-Ligand Binding by Protein O-Fucosyltransferase 1 and Fringe.J Biol Chem,2003;278:42340-42345.
  4. 4. Moloney DJ,Shair LH,Lu FM,et al.Mammalian Notch1 Is Modified with Two Unusual Forms of O-Linked Glycosylation Found on Epidermal Growth Factor-like Modules.J Biol Chem,2000,275:9604-9611.
  5. 5. Lei L,Xu A,Panin VM,et al.An O-fucose site in the ligand binding domain inhibits Notch activation,2003,130:6411-6421.
  6. 6. Xu A,Haines N,Dlugosz M.In Vitro Reconstitution of the Modulation of Drosophila Notch-Ligand Binding by Fringe.J Biol Chem,2007,282:35153-35162.
  7. 7. Yang LT,Nichols JT,Yao C,et al.Fringe Glycosyltransferases Differentially Modulate Notch1 Proteolysis Induced by Delta1 and Jagged1.Mol Biol Cell,2005,16:927-942.
  8. 8. 劉春濤,王曾禮,馮玉麟,等.哮喘動(dòng)物模型氣道中白細(xì)胞介素5和10的動(dòng)態(tài)變化及其意義.中華結(jié)核與呼吸雜志,2000;23:239-242.
  9. 9. 周敏,郭雪君,楊敏.支氣管哮喘BALB/c小鼠肺組織及肺T細(xì)胞中Notch1的表達(dá).上海交通大學(xué)學(xué)報(bào)（醫(yī)學(xué)版）,2007,27:161-164.
  10. 10. 楊敏,郭雪君,徐衛(wèi)國(guó)等.Notch配體在哮喘小鼠肺中的表達(dá).中國(guó)呼吸與危重監(jiān)護(hù)雜志,2007;6:257-230.
  11. 11. O′Byrne PM.Cytokines or Their Antagonists for the Treatment of Asthma.Chest,2006,130:244-250.
  12. 12. Pernis AB,Rothman PB.JAK-STAT signaling in asthma.J Clin Invest.2002,109:1279-1283.
  13. 13. Kheradmand F,Kiss A,Xu J,et al.A Protease-Activated Pathway Underlying Th Cell Type 2 Activation and Allergic Lung Disease1.J Immunol,2002,169:5904-5911.
  14. 14. Georas SN,Guo J,De Fanis U,et al.T-helper cell type-2 regulation in allergic disease.Eur Respir J,2005,26:1119-1137.
  15. 15. Gerard F.Hoyne Notch signaling in the immune system J.Leukoc.Biol.,Dec 2003,74:971.
  16. 16. Sun-Ok Yoon,Xin Zhang,Paul Berner,Bianca Blom,et al.Notch Ligands Expressed by Follicular Dendritic Cells Protect Germinal Center B Cells from Apoptosis J.Immunol.,Jul 2009,183:352 - 358.
  17. 17. Jonathon F.Hutton,Tessa Gargett,Timothy J.Sadlon,et al.Development of CD4+CD25+FoxP3+ regulatory T cells from cord blood hematopoietic progenitor cells J.Leukoc.Biol.,Mar 2009,85:445 - 451.
  18. 18. Amsen D,Blander JM,Lee G,et a1.Instruction of Distinct CD4 T Helper Cell Fates by Different Notch Ligands on Antigen-Presenting Cells.Cell,2004,ll7:515-526.
  19. 19. Amsen D,Antov A,Jankovic D,et al.Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch.Immunity,Jul 2007；27（1）:89-99.
  20. 20. Hozumi K,Abe N,Chiba S,et a1.Active form of notch member can enforce T lymphopoiesis on lymphoid progenitors in the monolayer culture specific for B cell development.J Immunol,2003,170:4973-4979.
  21. 21. Maekawa Y,Tsukumo S,Chiba H,et a1.Delta1-Notch3 Interactions Bias the Functional Differentiation of Activated CD4+ T Cells.Immunity,2003,19:549-559.
  22. 22. Shi S,Stanley P.Protein O-fucosyltransferase 1 is an essential component of Notch signaling pathways.PNAS.2003,100:5234-5239.
  23. 23. Okajima T,Irvine KD.Regulation of Notch Signaling by O-Linked Fucose.Cell,2002,111:893-904.
  24. 24. Ge CH,Stanley P.The O-fucose glycan in the ligand-binding domain of Notch1 regulates embryogenesis and T cell development.PNAS,2008,105:1539-1544.
  25. 25. Liangtung Y,James TN,Christine Y,et a1.Fringe Glycosyltransferases Differentially Modulate Notch1 Proteolysis Induced by Delta1 and Jagged1.Mol Biol Cell,2005,16:927-942.