人早胚间充质干细胞向毛囊上皮转变过程中JAM1、Tiam1与细胞极性形成的关系
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
目的:建立诱导人早胚间充质干细胞(hMSC)向毛囊上皮细胞分化的模型,初步实现裸鼠局部皮肤毛发的生成。分析hMSC向毛囊上皮细胞分化过程中连接黏附分子1(JAM1)、肿瘤细胞迁移因子(Tiam1)、非典型性磷酸化的蛋白激酶ζ(p-PKCζ)与极性蛋白3(PAR3)的关系,分析JAM1、Tiam1与细胞极性形成的关系。分析JAM1与毛囊生长方向和细胞极性形成的关系。
     方法:1.复苏hMSC和表皮干细胞,进行生物学特性和相关的安全性检测,随后进行大规模培养扩增。2.分离培养人毛乳头细胞(DP)并进行鉴定。3.DP细胞诱导hMSC,RT-PCR方法检测诱导后hMSC中DP细胞特异性分子SCF、ET-1和bFGF表达的变化。4.DP细胞诱导表皮干细胞,RT-PCR和Western-blotting方法检测诱导后表皮干细胞中uPA的变化。5.将一定数量的hMSC以皮下或皮内注射的方式移植到裸鼠皮肤组织中,H.E观察不同时间点毛囊生成情况,免疫组化检测HLA-1在不同时间点裸鼠新生毛囊中的表达,免疫组化分析角蛋白(K)和SM(smooth muscle)-a-actin在裸鼠新生毛囊中的表达。采用RNA干扰的方式抑制JAM1在hMSC中的表达,将干扰后的hMSC移植到裸鼠皮内,后续实验方法同正常hMSC移植裸鼠。6.激光共聚焦和Western-Blotting方法检测hMSC皮内移植后不同时间点裸鼠新生毛囊中JAM1、Tiam1、p-PKCζ和PAR3的表达并初步分析这些分子表达的位置关系和时间顺序。
     结果:1.hMSC以皮内注射的方式移植到裸鼠皮肤组织,可引起裸鼠皮肤局部毛发的生成。2.激光共聚焦结果显示在毛囊生成过程中,JAM1、PAR3和p-PKCζ的表达有很强的方向性,Tiam1表达均匀。Western-blotting结果显示,JAM1、PAR3、p-PKCζ和Tiam1的表达量逐渐增加。抑制JAM1在hMSC中的表达,其在裸鼠体内形成毛囊的能力下降。3.在成熟毛囊中,JAM1、PAR3和p-PKCζ分布在毛囊的根鞘处。4.DP细胞可诱导表皮干细胞往毛囊方向分化,可诱导hMSC表达DP细胞的特异性分子并表现DP细胞特有的凝集样生长。
     结论:hMSC可诱导并参与裸鼠毛发的生成。在毛发生成过程中,JAM1、PAR3、p-PKCζ的分布和位置关系与毛囊的生成方向和体积增加有密切关系,体现明显的方向性。p-PKCζ介导PAR3与Tiam1的反应。JAM1感受局部微环境中的信息而引发毛囊的生成和拓展,Tiam1作为极性相关分子的反应平台而维持毛囊上皮细胞的极性。
Objection: To construct a model of hMSC differentiate into epithelial cells from hair follicle (HF) and induce local skin hair follicle reformation. To detect the roles of JAM1; Tiam1; p-PKCζand PAR3 in the process of hMSC differentiate into epithelial cells. To find the relationships between JAM1; Tiam1 and cell polarition; hair follicle oritention.
     Methods: 1. Thawing hMSC, undertake cells biological character and pathogen detection, then large scale cultivation of cells for next experiment. 2. Isolation, culture and identification of human dermal papilla cells. 3. Using real-time polymerase chain reaction to detect the uPA expression in epidermal cells after human dermal papilla cells induced. 4. Xenografts were initiated by intracutaneous injection of 2×10~4 hMSC or hMSC with JAM1 RNAi. Haematoxylin & Eosin staining was used to detect hair follicle information in different time. 5. Observation of JAM1, PAR3, p-PKCζand Tiam1 by double immunofluorescense of different stage HF using laser scanning confocal microscopy. Western-blotting was used to detect the expression of JAM1, PAR3, p-PKCζand Tiam1 in different stage HF.
     Results: 1. Hair follicle formation was detected in local nude mice skin after human mesenchymal cell suspensions intracutaneous injection. 2. In the process of HF formation, it's showed that Tiam1 was expressed in all around cells of HF, however, JAM1, PAR3 and p-PKCζwere selectively expressed and enriched on the top of different development stages of HF. 3. JAM1, PAR3 and p-PKCζwere selectively expressed in the root sheath of mature haif follicle. 4. Dermal papilla cells can induce epidermal cells differentiate into hair follicle.
     Conclusion: hMSC can induce and participate in the HF formation in nude mice. In the process of HF formation, the expression of JAM1, PAR3 and p-PKCζwere selective. The selective expressions of JAM1, PAR3 and p-PKCζhave close relationship to the growth direction and volume increases of HF. p-PKCζare the regulator of PAR3 and Tiam1. JAM1 acceptance the messengers form the microenvironment of nude mice skin tissue and induce the hair follicle development and growth, Tiam1 is the platform of polarity molecular which play key role in the maintenance of hair follicle epithelial cell polarity.
引文
(1) Korbling M, Estrov Z. Adult stem cells for tissue repair - a new therapeutic concept? N Engl J Med. 2003 Aug 7; 349(6):570-582.
    (2) Yamaguchi Y, Yoshikawa K. Cutaneous wound healing: an update. J Dermatol. 2001 Oct; 28 (10): 521-34.
    (3) Jahoda CA, Reynolds AJ. Hair follicle dermal sheath cells: unsung participants in wound healing. Lancet. 2001 Oct 27;358(9291): 1445-8
    (4) Tolg C, Hamilton SR, Nakrieko KA. Rhamm-/- fibroblasts are defective in CD44-mediated ERK1, 2 motogenic signaling, leading to defective skin wound repair. J Cell Biol. 2006 Dec 18; 175(6): 1017-28.
    (5) Etienne-Manneville S, Hall A. Cdc42 regulates GSK-3beta and adenomatous polyposis coli to control cell polarity. Nature. 2003 Feb 13; 421(6924):753-6.
    (6) Bjorkoy G, Perander M, Overvatn A, Johansen T. Reversion of Ras- and phosphatidyl- choline-hydrolyzing phospholipase C-mediated transformation of NIH 3T3 cells by a dominant interfering mutant of protein kinase C lambda is accompanied by the loss of constitutive nuclear mitogen-activated protein kinase/extracellular signal-regulated kinase activity. J Biol Chem. 1997 Apr 25; 272(17):11557-65.
    (7) Joberty G, Petersen C, Gao L, Macara IG. The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42. Nat Cell Biol. 2000 Aug; 2(8):531-9.
    (8) Naik MU, Naik UP. Junctional adhesion molecule-A-induced endothelial cell migration on vitronectin is integrin alpha v beta 3 specific. J Cell Sci. 2006 Feb 1; 119(Pt 3):490-9.
    (9) Aurrand-Lions M, Duncan L, Ballestrem C, Imhof BA. JAM-2, a novel immunoglobulin superfamily molecule, expressed by endothelial and lymphatic cells. J Biol Chem. 2001 Jan 26; 276(4):2733-41.
    (10) Aurrand-Lions MA, Duncan L, Du Pasquier L, Imhof BA. Cloning of JAM-2 and JAM-3: an emerging junctional adhesion molecular family? Curr Top Microbiol Immunol. 2000; 251:91-8.
    (11) Palmeri D, van Zante A, Huang CC, Hemmerich S, Rosen SD. Vascular endothelial junction-associated molecule, a novel member of the immunoglobulin superfamily, is localized to intercellular boundaries of endothelial cells. J Biol Chem. 2000 Jun 23;275(25): 19139-45.
    (12) Malergue F, Galland F, Martin F, Mansuelle P, Aurrand-Lions M, Naquet P. A novel immunoglobulin superfamily junctional molecule expressed by antigen presenting cells, endothelial cells and platelets. Mol Immunol. 1998 Dec; 35(17):1111-9.
    (13) Williams LA, Martin-Padura I, Dejana E, Hogg N, Simmons DL. Identification and characterisation of human Junctional Adhesion Molecule (JAM). Mol Immunol. 1999 Dec; 36(17): 1175-88.
    (14) Habets GG, Scholtes EH, Zuydgeest D, van der Kammen RA, Stam JC, Berns A, and Collard JG Identification of an invasion-inducing gene, Tiam-1, that encodes a protein with homology to GDP-GTP exchangers for Rho-like proteins. Cell. 1994 May 20; 77(4):537-49.
    (15) Minard ME, Herynk MH, Collard JG, Gallick GE. The guanine nucleotide exchange factor Tiaml increases colon carcinoma growth at metastatic sites in an orthotopic nude mouse model. Oncogene. 2005 Apr 7; 24(15):2568-73.
    (16) Habets GG, van der Kammen RA, Stam JC, Michiels F, Collard JG Sequence of the human invasion-inducing TIAM1 gene, its conservation in evolution and its expression in tumor cell lines of different tissue origin. Oncogene. 1995 Apr 6;10(7):1371-6.
    (17) Mertens AE, Pegtel DM, Collard JG Tiaml takes PARt in cell polarity. Trends Cell Biol. 2006 Jun;16(6):308-16.
    (18) Minard ME, Ellis LM, Gallick GE. Tiaml regulates cell adhesion, migration and apoptosis in colon tumor cells. Clin Exp Metastasis. 2006;23(5-6):301-13.
    (19) Michiels F, Habets GG, Stam JC, van der Kammen RA, Collard JG. A role for Rac in Tiaml-induced membrane ruffling and invasion. Nature. 1995 May 25;375(6529):338-40.
    (20) Tumbar T, Guasch G, Greco V, Blanpain C, Lowry WE, Rendl M, Fuchs E. Defining the epithelial stem cell niche in skin. Science. 2004 Jan 16;303(5656):359-63. Epub 2003 Dec 11.
    (21) Blanpain C,Lowry WE,Geoghegan A,Polak L,Fuchs E.Self-renewal,multipotency,and the existence of two cell populations within an epithelial stem cell niche.Cell.2004 Sep 3;118(5):635-48.
    (22) 仵敏娟,刘善荣,刘厚奇。人早期胚胎间充质干细胞的定位和体外初步分离培养.第二军医大学学报.2004 25(8):818-821.
    (23) Alonso L,Fuchs E.The hair cycle.J Cell Sci.2006 Feb 1;119(Pt 3):391-3.
    (24) Jaroslav Stark,Thomas and,and Sarah E.Millar.Hairy Math:Insights into Hair-Follicle Spacing and Orientation。Cell 128,January 12,2007.17-20.
    (25) George Cotsarelis.Gene expression profiling gets to the root of human hair follicle stem cells.J.Clin.Invest.116(1):19-22(2006).doi:10.1172/JCI27490.
    (26) Wu M,Yang L,Liu S,Li H,Hui N,Wang F,Liu H.Differentiation potential of human embryonic mesenchymal stem cells for skin-related tissue.Br J Dermatol.2006 Aug;155(2):282-91.
    (27) 呼莹,马丽,马冠杰等。成人和胎儿骨髓间充质干细胞的比较研究。中华血液学杂志,2002.23:645-648。
    (28) Feridoun Babai,Javid Musevi-Aghdam,Walter Schurch,Andre Royal and Giulio Gabbiani.Coexpression of a-sarcomeric actin,a-smooth muscle actin and desmin during myogenesis in rat and mouse embryos I.Skeletal muscle.Volume 44 Issue 2 Page 132-142,August 1990
    (29) Greenburg G,Hay ED.Epithelia suspended in collagen gels can lose polarity and express characteristics of migrating mesenchymal cells.J Cell Biol.1982Oct;95(1):333-9.
    (30) Michel M,Torok N,Godbout MJ,Lussier M,Gaudreau P,Royal A,Germain L.Keratin 19 as a biochemical marker of skin stem cells in vivo and in vitro:keratin 19 expressing cells are differentially localized in function of anatomic sites,and their number varies with donor age and culture stage.J Cell Sci.1996 May;109(Pt 5):1017-28.
    (31) Jensen PJ,Lavker RM.Urokinase is a positive regulator of epidermal proliferation in vivo.J Invest Dermatol.1999 Feb;112(2):240-4.
    (32) Cui ZH,Yang T,GAO QG,Wang Y.Urokinase plasminogen activator(uPA)is a positive regulator of outer root sheath keratinocyte proliferation.1:Cell Biol Int.2004;28(8-9):571-5.
    (33) Andrei A. Panteleyev, Colin A. B. Jahoda and Angela M. Christiano. Hair follicle predetermination. Journal of Cell Science 114, 3419-3431 (2001)
    (34) U. Tepass, G.Tanentzapf, R. Ward and R. Fehon, Epithelial cell polarity and cell junctions in Drosophila, Annu. Rev. Genet. 35 (2001), pp. 747-784. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (176)
    (35) Helfrich I, Schmitz A, Zigrino P, Michels C, Haase I, le Bivic A, Leitges M, Niessen CM. Role of aPKC isoforms and their binding partners Par3 and Par6 in epidermal barrier formation. J Invest Dermatol. 2007 Apr;127(4):782-91. Epub 2006 Nov 16.
    (36) Dalous J, Burghardt E, Miiller-Taubenberger A, Bruckert F, Gerisch G, Bretschneider T. Reversal of cell polarity and actin-myosin cytoskeleton reorganization under mechanical and chemical stimulation. Biophys J. 2008 Feb l;94(3):1063-74. Epub 2007 Sep 28.
    (37) Poujade M, Grasland-Mongrain E, Hertzog A, Jouanneau J, Chavrier P, Ladoux B, Buguin A, Silberzan P. Collective migration of an epithelial monolayer in response to a model wound. Proc Natl Acad Sci U S A. 2007 Oct 9; 104(41):15988-93.
    (38) Jamora C, DasGupta R, Kocieniewski P, Fuchs E. Links between signal transduction, transcription and adhesion in epithelial bud development. Nature. 2003 Mar 20;422(6929):317-22.
    (39) Kemphues KJ, Priess JR, Morton DG, Cheng NS. Identification of genes required for cytoplasmic localization in early C. elegans embryos. Cell. 1988 Feb 12;52(3):311-20.
    (40) Shin K, Fogg VC, Margolis B. Shin K, Fogg VC, Margolis B. Tight junctions and cell polarity. Annu Rev Cell Dev Biol. 2006;22:207-35.
    (41) Drubin DG, Nelson WJ. Origins of cell polarity. Cell. 1996 Feb 9;84(3):335-44.
    (42) Lin D, Edwards AS, Fawcett JP, Mbamalu G, Scott JD, Pawson T. A mammalian PAR-3-PAR-6 complex implicated in Cdc42/Racl and aPKC signalling and cell polarity. Nat Cell Biol. 2000 Aug; 2(8):540-7.
    (43) Joberty G, Petersen C, Gao L, Macara IG. The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42. Nat Cell Biol. 2000 Aug;2(8):531-9.
    (44) Etienne-Manneville S, Hall A. Cdc42 regulates GSK-3beta and adenomatous polyposis coli to control cell polarity. Nature. 2003 Feb 13; 421(6924):753-6. Epub 2003 Jan 29.
    (45) Naik MU, Naik UP. Junctional adhesion molecule-A-induced endothelial cell migration on vitronectin is integrin alpha v beta 3 specific. J Cell Sci. 2006 Feb 1;119(Pt 3):490-9.
    (46) Aurrand-Lions M, Duncan L, Ballestrem C, Imhof BA. JAM-2, a novel immunoglobulin superfamily molecule, expressed by endothelial and lymphatic cells. J Biol Chem. 2001 Jan 26;276(4):2733-41.
    (47) Aurrand-Lions MA, Duncan L, Du Pasquier L, Imhof BA. Cloning of JAM-2 and JAM-3: an emerging junctional adhesion molecular family? Curr Top Microbiol Immunol. 2000; 251:91-8.
    (48) Palmeri D, van Zante A, Huang CC, Hemmerich S, Rosen SD. Vascular endothelial junction-associated molecule, a novel member of the immunoglobulin superfamily, is localized to intercellular boundaries of endothelial cells. J Biol Chem. 2000 Jun 23;275(25):19139-45.
    (49) Malergue F, Galland F, Martin F, Mansuelle P, Aurrand-Lions M, Naquet P. A novel immunoglobulin superfamily junctional molecule expressed by antigen presenting cells, endothelial cells and platelets. Mol Immunol. 1998 Dec;35(17):1111-9.
    (50) Williams LA, Martin-Padura I, Dejana E, Hogg N, Simmons DL. Identification and characterisation of human Junctional Adhesion Molecule (JAM). Mol Immunol. 1999 Dec; 36(17):1175-88.
    (51) Thomas FC, Sheth B, Eckert JJ, Bazzoni G, Dejana E, Fleming TP. Contribution of JAM-1 to epithelial differentiation and tight-junction biogenesis in the mouse preimplantation embryo.J Cell Sci. 2004 Nov l;117(Pt 23):5599-608.
    (52) Naik MU, Mousa SA, Parkos CA, Naik UP. Signaling through JAM-1 and α v83 is required for the angiogenic action of bFGF: dissociation of the JAM-1 and αvβ3 complex. Blood 2003;102:2108-14.
    (53) Naik MU, Vuppalanchi D, Naik UP. Essential role of junctional adhesion molecule-1 in basic fibroblast growth factor-induced endothelial cell migration. Arterioscler Thromb Vasc Biol 2003;23:2165-71.
    (54) Cooke VG,Naik MU,Skarnes W,Naik UP.Essential Role of Junctional Adhesion Molecule-A in bFGF-Induced Angiogenesis.Journal of Thrombosis and Haemostasis 2005;Volume 3,Supplement 1:abstract number.
    (55) Habets GG,Scholtes EH,Zuydgeest D,van der Kammen RA,Stare JC,Berns A,and Collard JG.Identification of an invasion-inducing gene,Tiam-1,that encodes a protein with homology to GDP-GTP exchangers for Rho-like proteins.Cell.1994 May 20;77(4):537-49.
    (56) Minard ME,Herynk MH,Collard JG,Gallick GE.The guanine nucleotide exchange factor Tiaml increases colon carcinoma growth at metastatic sites in an orthotopic nude mouse model.Oncogene.2005 Apr 7;24(15):2568-73.
    (57) Shibata K,Nishimura J,Yufu Y,Nawata H.Alterations in thrombin-induced protein tyrosine phosphorylation of platelets from patients with chronic myelogenous leukemia.Int J Hematol.1992 Apr;55(2):189-96.
    (58) Mertens AE,Pegtel DM,Collard JG.Tiaml takes PARt in cell polarity.Trends Cell Biol.2006 Jun;16(6):308-16.
    (59) Mertens AE,Rygiel TP,Olivo C,van der Kammen R,Collard JG.The Rac activator Tiaml controls tight junction biogenesis in keratinocytes through binding to and activation of the Par polarity complex.J Cell Biol.2005 Sep 26;170(7):1029-37.
    (60) Minard ME,Ellis LM,Gallick GE.Tiaml regulates cell adhesion,migration and apoptosis in colon tumor cells.Clin Exp Metastasis.2006;23(5-6):301-13.
    (61) Wang Y,Du D,Fang L,Yang G,Zhang C,Zeng R,Ullrich A,Lottspeich F,Chert Z.Tyrosine phosphorylated Par3 regulates epithelial tight junction assembly promoted by EGFR signaling.EMBO J.2006 Nov 1;25(21):5058-70.Epub 2006 Oct 19.
    (62) Elbashir SM,Harborth J,Lendeckel W,Yalcin A,Weber K,Tuschl T.Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells.Nature.2001 May 24;411(6836):494-8.
    (63) 廖端芳,关永源.蛋白激酶-ζ的研究进展[J].中国药理学通报,2002,18(1):13-16。
    (64) 徐竞,刘良明.参与失血性休克血管钙敏感性调节的信号分子[J].中国病理生理杂志,2006,22(5):896-899。
    (65) Rendl M,Lewis L,Fuchs E.Molecular dissection of mesenchymal-epithelial interactions in the hair follicle.PLoS Biol.2005 Nov;3(11):e331.Epub 2005Sep 20.
    (66) 钟白玉 杨卫兵 杨希川 郝飞 伍津津.二步酶消化法分离人头皮毛乳头细胞.《中华皮肤科杂志.2003年36卷7期.406-410。
    (67) Jahoda CA,Horne KA,Oliver RF.Induction of hair growth by implantation of cultured dermal papilla cells.Nature.1984 Oct 11-17;311(5986):560-2.
    (68) Messenger AG.The culture of dermal papilla cells from human hair follicles.Br J Dermatol.1984 Jun;110(6):685-9.
    (69) Roh C,Tao Q,Lyle S.Dermal papilla-induced hair differentiation of adult epithelial stem cells from human skin._Physiol Genomics.2004 Oct 4;19(2):207-17.Epub 2004 Aug 3.
    (70) Kishimoto J,Ehama R,Wu L,Jiang S,Jiang N,Burgeson RE.Selective activation of the versican promoter by epithelial- mesenchymal interactions during hair follicle development.Proc Natl Acad Sci U S A.1999 Jun 22;96(13):7336-41.
    (71) Jahoda CA,Oliver RF.Vibrissa dermal papilla cell aggregative behaviour in vivo and in vitro._J Embryol Exp Morphol.1984 Feb;79:211-24.
    (72) Lu,Z.F.Cai,S.Q.Wu,J.J.Zheng,M.(2006).Biological characterization of cultured dermal papilla cells and hair follicle regeneration in vitro and in vivo.Chin Med J(Engl.119,275-81.
    (73) Huang EY,Wu H,Island ER,Chong SS,Warburton D,Anderson KD,Tuan TL.Differential expression of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 in early and late gestational mouse skin and skin wounds.Wound Repair Regen.2002 Nov-Dec;10(6):387-96.
    (74) Plekhanova OS,Stepanova VV,Ratner EI,Bobik A,Tkachuk VA,Parfyonova YV.Urokinase plasminogen activator in injured adventitia increases the number of myofibroblasts and augments early proliferation._J Vasc Res.2006;43(5):437-46.Epub 2006 Aug 7.
    (75) Carney TJ,von der Hardt S,Sonntag C,Amsterdam A,Topczewski J,Hopkins N,Hammerschmidt M.Inactivation of serine protease Matriptasela by its inhibitor Hail is required for epithelial integrity of the zebrafish epidermis._Development.2007 Oct;134(19):3461-71.Epub 2007 Aug 29.
    (76) Cotsarelis G. Sun TT, Lavker R M. Label-retaining cells in the bulge area of pilosebaceous unit: im placations for follicle stem cells, hair cycle, and skin carcinogenesis.Cell, 1990, 61: 1329.
    (77) Romer J, Lund L R, Eriksen J, et al. Differential expression of urokinase-type plasminogen activator and type-linhibitor during healing of mouse skin wounds. J Invest Dermatol, 1991, 97: 803.
    (78) Gao L, Macara IG Isoforms of the polarity protein par6 have distinct functions. J Biol Chem. 2004 Oct 1; 279(40):41557-62. Epub 2004 Jul 28.
    (79) Macara IG Par proteins: partners in polarization. Curr Biol. 2004 Feb 17; 14(4):R160-2.
    (80) Macara IG Parsing the polarity code. Nat Rev Mol Cell Biol. 2004 Mar;5(3):220-31.
    (81) Joberty G, Petersen C, Gao L, Macara IG The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42. Nat Cell Biol. 2000 Aug;2(8):531-9.
    (82) Lin D, Edwards AS, Fawcett JP, Mbamalu G, Scott JD, Pawson T. A mammalian PAR-3-PAR-6 complex implicated in Cdc42/Racl and aPKC signalling and cell polarity. Nat Cell Biol. 2000 Aug;2(8):540-7.
    (83) Wodarz A, Ramrath A, Grimm A, Knust E. Drosophila atypical protein kinase C associates with Bazooka and controls polarity of epithelia and neuroblasts. J Cell Biol. 2000 Sep 18; 150(6):1361-74.
    (84) Wodarz A. Tumor suppressors: linking cell polarity and growth control. Curr Biol. 2000 Sep 7; 10(17):R624-6.
    (85) Petronczki M, Knoblich JA. DmPAR-6 directs epithelial polarity and asymmetric cell division of neuroblasts in Drosophila. Nat Cell Biol. 2001 Jan; 3(l):43-9.
    (86) Tanentzapf G, Smith C, McGlade J, Tepass U. Apical, lateral, and basal polarization cues contribute to the development of the follicular epithelium during Drosophila oogenesis. J Cell Biol. 2000 Nov 13; 151(4):891-904.
    (87) Bachmann A, Schneider M, Theilenberg E, Grawe F, Knust E. Drosophila Stardust is a partner of Crumbs in the control of epithelial cell polarity. Nature. 2001 Dec 6; 414(6864):638-43.
    (88) Medina E, Williams J, Klipfell E, Zarnescu D, Thomas G, Le Bivic A. Crumbs interacts with moesin and beta(Heavy)-spectrin in the apical membrane skeleton of Drosophila.J Cell Biol.2002 Sep 2;158(5):941-51.Epub 2002 Sep 3.
    (89) Bilder D,Li M,Perrimon N.Cooperative regulation of cell polarity and growth by Drosophila tumor suppressors.Science.2000 Jul 7;289(5476):113-6.
    (90) Etienne-Manneville S,Hall A.Rho GTPases in cell biology.Nature.2002Dec 12;420(6916):629-35.
    (91) Lian WN,Wu TW,Dao RL,Chen YJ,Lin CH.Deglycosylation of Na+/K+-ATPase causes the basolateral protein to undergo apical targeting in polarized hepatic cells.J Cell Sci.2006 Jan 1;119(Pt 1):11-22.Epub 2005Dec 8.
    (92) Breuza L,Garcia M,Delgrossi MH,Le Bivic A.Role of the membrane-proximal O-glycosylation site in sorting of the human receptor for neurotrophins to the apical membrane of MDCK cells.Exp Cell Res.2002Feb 15;273(2):178-86.
    (93) Spodsberg N,Alfalah M,Naim HY.Characteristics and structural requirements of apical sorting of the rat growth hormone through the O-glycosylated stalk region of intestinal sucrase-isomaltase.J Biol Chem.2001 Dec 7;276(49):46597-604.
    (94) Delacour D,Cramm-Behrens CI,Drobecq H,Le Bivic A,Naim HY,Jacob R.Requirement for galectin-3 in apical protein sorting.Curr Biol.2006 Feb 21;16(4):408-14.
    (95) Gut A,Kappeler F,Hyka N,Balda MS,Hauri HP,Matter K.Carbohydrate-mediated Golgi to cell surface transport and apical targeting of membrane proteins.EMBO J.1998 Apr 1;17(7):1919-29.
    (96) 王向阳 聂静 孙惠力 骆宁 董秀清 刘伟 余学清.Par-3蛋白在转化生长因子β1介导的大鼠肾小管上皮细胞转分化中的作用.《中华肾脏病杂志》-2007年23卷7期 442-447.
    (97) Hammerton RW,Krzeminski KA,Mays RW,Ryan TA,Wollner DA,Nelson WJ.Mechanism for regulating cell surface distribution of Na+,K(+)-ATPase in polarized epithelial cells.Science.1991 Nov 8;254(5033):847-50.
    (98) Marrs JA,Andersson-Fisone C,Jeong MC,Cohen-Gould L,Zurzolo C,Nabi IR, Rodriguez-Boulan E, Nelson WJ. Plasticity in epithelial cell phenotype: modulation by expression of different cadherin cell adhesion molecules. J Cell Biol. 1995 Apr; 129(2):507-19.
    (99) Orsulic S, Huber 0, Aberle H, Arnold S, Kemler R. E-cadherin binding prevents beta-catenin nuclear localization and beta-catenin/LEF-1-mediated transactivation. J Cell Sci. 1999 Apr; 112 (Pt 8):1237-45.
    (100) Miyoshi K, Shillingford JM, Le Provost F, Gounari F, Bronson R, von Boehmer H, Taketo MM, Cardiff RD, Hennighausen L, Khazaie K. Activation of beta -catenin signaling in differentiated mammary secretory cells induces transdifferentiation into epidermis and squamous metaplasias. Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):219-24. Epub 2002 Jan 2.
    (101) Hanks SK, Polte TR. Signaling through focal adhesion kinase. Bioessays. 1997 Feb; 19(2): 137-45.
    (102) Stupack DG, Cheresh DA. Get a ligand, get a life: integrins, signaling and cell survival. J Cell Sci. 2002 Oct 1; 115(Pt 19):3729-38.
    (103) Korbling M, Estrov Z. Adult stem cells for tissue repair - a new therapeutic concept? N Engl J Med. 2003 Aug 7; 349(6):570-582.
    (104) Yamaguchi Y, Yoshikawa K. Cutaneous wound healing: an update. J Dermatol. 2001 Oct; 28 (10): 521-34.
    (105) Jahoda CA, Reynolds AJ. Hair follicle dermal sheath cells: unsung participants in wound healing. Lancet. 2001 Oct 27;358(9291): 1445-8
    (106) Tolg C, Hamilton SR, Nakrieko KA. Rhamm-/- fibroblasts are defective in CD44-mediated ERK1, 2 motogenic signaling, leading to defective skin wound repair. J Cell Biol. 2006 Dec 18; 175(6):1017-28.
    (107) Etienne-Manneville S, Hall A. Cdc42 regulates GSK-3beta and adenomatous polyposis coli to control cell polarity. Nature. 2003 Feb 13; 421(6924):753-6.
    (108) Bjorkoy G, Perander M, Overvatn A, Johansen T. Reversion of Ras- and phosphatidyl- choline-hydrolyzing phospholipase C-mediated transformation of NIH 3T3 cells by a dominant interfering mutant of protein kinase C lambda is accompanied by the loss of constitutive nuclear mitogen-activated protein kinase/extracellular signal-regulated kinase activity. J Biol Chem. 1997 Apr 25; 272(17): 11557-65.
    (109) Joberty G, Petersen C, Gao L, Macara IG. The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42. Nat Cell Biol. 2000 Aug; 2(8):531-9.
    (110) Tsukita S, Furuse M, Itoh M. Structural and signalling molecules come together at tight junctions. Curr Opin Cell Biol. 1999 Oct; ll(5):628-33.
    (111) Tsukita S, Furuse M, Itoh M. Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol. 2001 Apr; 2(4):285-93.
    (112) Rollins BJ. Chemokines. Blood. 1997 Aug 1; 90(3):909-28.
    (113) Amado LC, Saliaris AP, Schuleri KH, St John M, Xie JS, Cattaneo S, Durand DJ, Fitton T, Kuang JQ, Stewart G, Lehrke S, Baumgartner WW, Martin BJ, Heldman AW, Hare JM. Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. Proc Natl Acad Sci U S A. 2005 Aug 9; 102(32):11474-9. Epub 2005 Aug 1.
    (114) Ying QL, Nichols J, Evans EP, Smith AG Changing potency by spontaneous fusion. Nature. 2002 Apr 4; 416(6880):545-8. Epub 2002 Mar 13.
    (115) Uccelli A, Moretta L, Pistoia V. Immunoregulatory function of mesenchymal stem cells. Eur J Immunol 2006; 36:2566-2573.
    (116) Di Nicola M, Carlo-Stella C,Magni M,et al.Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli.Blood 2002;99:3838-3843.
    (117) Plumas J,Chaperot L, Richard MJ.Mesenchymal stem cells induce apoptosis of activated T cells.Leukemia 2005;19(9):1597-1604.
    (118) Yang CC, Lin SD, Yu HS. Effect of growth factors on dermal fibroblast contraction in normal skin and hypertrophic scar. J Dermatol Sci. 1997 Feb; 14(2): 162-9.
    (119) Stitziel NO, Mar BG, Liang J, Westbrook CA. Membrane-associated and secreted genes in breast cancer. Cancer Res. 2004 Dec 1; 64(23):8682-7.
    (120) Ponte P, Sun-yu N, Engel J, et al. Evolutionary conservation in the untranslated regions of actin mRNAs: DNA sequence of a human beta-actin cDNA. Nucleic Acids Research, 1984,12(3) : 1687-1696.
    (121) Mandell KJ, Babbin BA, Nusrat A, Parkos CA. Junctional adhesion molecule 1 regulates epithelial cell morphology through effects on betal integrins and Rapl activity. J Biol Chem. 2005 Mar 25; 280(12):11665-74. Epub 2005 Jan 27.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700