肠上皮细胞紧密连接在肠屏障中的作用研究进展
秦环龙, 高志光, 上海交通大学附属第六人民医院外科 上海市 200233
国家自然科学基金项目,No. 30271286, 30471687
秦环龙,男, 1965-11-13生, 江苏省张家港人,汉族,上海交通大学外科学教授,主任医师, 博士,硕士生导师,现为上海交通大学附属第六人民医院副院长,肠外与肠内营养研究室主任,主要从事胃肠外科及临床营养研究工作.
项目负责人:秦环龙, 200233, 上海市宜山路600号, 上海交通大学附属第六人民医院外科. sshosp@public.sta.net.cn
电话:021-64942226 传真: 021-64368920
, http://www.100md.com
收稿日期:2005-01-06 接受日期: 2005-01-20
摘要肠上皮细胞紧密连接是肠上皮细胞间的主要连接方式，对维持上皮细胞极性及调节肠屏障的通透性发挥着重要的作用.因此，维持完整的肠上皮结构和功能对于保护肠道屏障功能、防止细菌内毒素及毒性大分子物质进入体内具有重要意义.本文从紧密连接在肠上皮中的生物学功能、分子调控机制及当前研究现状等作综合阐述.
关键词:肠上皮细胞;紧密连接; 黏膜屏障
秦环龙,高志光. 肠上皮细胞紧密连接在肠屏障中的作用研究进展.世界华人消化杂志 2005;13(4):443-447
Furuse M, Fujita K, Hiiragi T, Fujimoto K, Tsukita S. Claudin-1 and-2: novel integral membrane proteins localizing at
, 百拇医药
tight junctions with no sequence similarityto occluding. J Cell Biol 1998;141:1539-1550
2 Matsuda M, Kubo A, Furuse M, Tsukita S. A peculiar internalizationof claudins, tight junction-specific adhesion
molecules, during the intercellularmovement of epithelial cells. J Cell Sci 2004;117(pt7):1247-1257
3 Yeaman C, Grindstaff KK, Nelson WJ. New perspective on mechanismsinvolved in generating epithelial cell polarity.
, 百拇医药
Physiol Rev 1999;79:73-98
4 Citi S, Denisenko N. Phosphorylation of the tight junction proteincingulin and the effects of protein kinase inhibitors
and activators in MDCK epithelial cells. JCell Sci 1995;108(pt8):2917-2926
5 Tsukita S, Furuse M. Occludin and claudins in tight-junctionstrands:leading or supporting players?
Trends Cell Biol 1999;9:268-273
, 百拇医药
6 Morita K, Huruse M, Fujimoto K, Tsukita S. Claudin multigene familyencoding four-transmembrane domain protein
components of tight junction strands. ProcNatl Acad Sci USA 1999;96:511-516
7 Citi S, Sabanay H, Jakes R, Geiger B, Kendrick-Jones J. Cingulin, anew peripheral component of tight junctions.
Nature 1988;333:272-276
8 Keon BH, Schafer S, Kuhn C, Grund C, Franke WW. Symplekin, a noveltype of tight junction plaque protein.
, http://www.100md.com
J Cell Biol 1996;134:1003-1018
9 Zhong Y, Saitoh T, Minase T, Sawada N, Enomoto K, Mori M.Monoclonal antibody 7H6 reacts with a novel tight
junction-associated protein distinct fromZO-1, cingulin and ZO-2. J Cell Biol 1993;120:477-483
10 Weber E, Berta G, Tousson A, St John P, Green MW, Gopalokrishnan U,Jilling T, Sorscher EJ, Elton TS, Abrahamson
DR. Expression and polarizedtargeting of a rab3 isoform in epithelial cells. J Cell Biol 1994;125:583-594
, http://www.100md.com
11 Martin-Padura I, Lostaglio S, Schneemann M, Williams L, Romano M,Fruscella P, Panzeri C, Stoppacciaro A, Ruco L,Villa A, Simmons D, Dejana E.Junctional adhesion molecule, a novel member of the immunoglobulinsuperfamily that
distributes at intercellularjunctions and modulates monocyte transmigration. J Cell Biol 1998;142:117127
12 Madara JL. Intestinal absorptive cell tight junctions are linked tocytoskeleton. Am J Physiol 1987;253(1pt1):C171-C175
, 百拇医药
13 van Meer G, Simons K. The function of tight junctions inmaintaining differences in lipid composition between the
apical and the basolateral cellsurface domains of MDCK cells. EMBO J 1986;5:1455-1464
14 Hauser H, Howell K, Dawson RM, Bowyer DE. Rabbit small intestinalbrush border membrane preparation and lipid
composition. Biochim Biophys Acta 1980;602:567-577
, http://www.100md.com
15 Ebnet K, Aurrand-Lions M, Kuhn A, Kiefer F, Butz S, Zander K, Meyerzu Brickwedde MK, Suzuki A, Imhof BA,Vestweber D. The junctional adhesionmolecule (JAM) family members JAM-2 and JAM-3 associate with the cell
polarity protein PAR-3: a possiblerole for JAMs in endothelial cell polarity. J Cell Sci 2003;116(pt19):3879-3891
16 Hollander D, Vadheim CM, Brettholz E, Petersen GM, Delahunty T,Rotter J. Increased intestinal permeability in
, http://www.100md.com
patients with Crohn's disease andtheir relatives. Ann Intern Med 1986;105:883-885
17 Bjarnason I. Intestinal permeability. Gut 1994;35(1Suppl):S18-S22
18 Yamaguchi Y, Dalle-Molle E, Hardison WG. Vasopressin and A23187stimulate phosphorylation of myosin light chain-1
in isolated rat hepatocytes. Am JPhysiol 1991;261(2pt1):G312-G319
19 Behrens J, Vakaet L, Friis R, Winterhager E, Van Roy F, Mareel MM,Birchmeier W. Loss of epithelial differentiation
, 百拇医药
and gain of invasivenesscorrelates with tyrosine phosphorylation of the E-cadherin/beta-catenincomplex in
cells transformed with atemperature-sensitive v-SRC gene. J Cell Biol 1993;120:757 -766
20 Meyer TN, Hunt J, Schwesinger C, Denker BM. Ga12regulates epithelial cell junctions through Src tyrosine kinases.
Am J Physiol Cell Physiol 2003;285:C1281-C1293
, 百拇医药 21 Gopalakrishnan S, Raman N, Atkinson SJ, Marrs JA. Rho GTPasesignaling regulates tight junction assembly and
protects tight junctions during ATPdepletion. Am J Physiol 1998;275(3pt1):C798-C809
22 Hopkins AM, Walsh SV, Verkade P, Boquet P, Nusrat A. Constitutiveactivation of Rho proteins by CNF-1 influences
tight junction structure andepithelial barrier function. J Cell Sci 2003;116(pt4):725-742
, 百拇医药
23 Tavelin S, Hashimoto K, Malkinson J, Lazorova L, Toth I, ArturssonP. A new principle for tight junction modulation
based on occludin peptides. MolPharmacol 2003;64:1530-1540
24 Rao JN, Li L, Golovina VA, Platoshyn O, Strauch ED, Yuan J X, WangJY. Ca2+-RhoAsignaling pathway required
for polyamine-dependent intestinalepithelial cell migration. Am J Physiol Cell Physiol 2001;280:C993-C1007
, http://www.100md.com
25 Mankertz J, Hillenbrand B, Tavalali S, Huber O, Fromm M, SchulzkeJ. Functional crosstalk between Wnt signaling
and Cdx-related transcriptionalactivation in the regulation of the claudin-2 promoter activity.
Biochem Biophys Res Commun 2004;314:10011007
26 Abbott A. Microbiology:gut reaction. Nature 2004;427:284-286
27 Hirano J, Yoshida T, Sugiyama T, Koide N, Mori I, Yokochi T. Theeffect of Lactobacillus rhamnosus on
, 百拇医药
enterohemorrhagic Escherichia coliinfection of human intestinal cells in vitro.
Microbiol Immunol 2003;47:405-409
28 Berkes J, Viswanathan VK, Savkovic SD, Hecht G. Intestinalepithelial responses to enteric pathogens:effects on the
tight junction barrier, iontransport, and inflammation. Gut 2003;52:439-451
29 Resta-Lenert S, Barrett K E. Live probiotics protect intestinalepithelial cells from the effects of infection with
, 百拇医药
enteroinvasive Escherichia coli(EIEC).Gut 2003;52:988-997
30 Yan F, Polk DB. Probiotic bacterium prevents cytokine-inducedapoptosis in intestinal epithelial cells.
J Biol Chem 2002;277:50959-50965
31 Michail S, Abernathy F. Lactobacillus plantarum reduces the invitro secretory response of intestinal epithelial cells
to enteropathogenic Escherichia coliinfection. J Pediatr Gastroenterol Nutr 2002;35:350-355
编辑 张海宁, 百拇医药( 秦环龙, 高志光)
国家自然科学基金项目,No. 30271286, 30471687
秦环龙,男, 1965-11-13生, 江苏省张家港人,汉族,上海交通大学外科学教授,主任医师, 博士,硕士生导师,现为上海交通大学附属第六人民医院副院长,肠外与肠内营养研究室主任,主要从事胃肠外科及临床营养研究工作.
项目负责人:秦环龙, 200233, 上海市宜山路600号, 上海交通大学附属第六人民医院外科. sshosp@public.sta.net.cn
电话:021-64942226 传真: 021-64368920
, http://www.100md.com
收稿日期:2005-01-06 接受日期: 2005-01-20
摘要肠上皮细胞紧密连接是肠上皮细胞间的主要连接方式，对维持上皮细胞极性及调节肠屏障的通透性发挥着重要的作用.因此，维持完整的肠上皮结构和功能对于保护肠道屏障功能、防止细菌内毒素及毒性大分子物质进入体内具有重要意义.本文从紧密连接在肠上皮中的生物学功能、分子调控机制及当前研究现状等作综合阐述.
关键词:肠上皮细胞;紧密连接; 黏膜屏障
秦环龙,高志光. 肠上皮细胞紧密连接在肠屏障中的作用研究进展.世界华人消化杂志 2005;13(4):443-447
Furuse M, Fujita K, Hiiragi T, Fujimoto K, Tsukita S. Claudin-1 and-2: novel integral membrane proteins localizing at
, 百拇医药
tight junctions with no sequence similarityto occluding. J Cell Biol 1998;141:1539-1550
2 Matsuda M, Kubo A, Furuse M, Tsukita S. A peculiar internalizationof claudins, tight junction-specific adhesion
molecules, during the intercellularmovement of epithelial cells. J Cell Sci 2004;117(pt7):1247-1257
3 Yeaman C, Grindstaff KK, Nelson WJ. New perspective on mechanismsinvolved in generating epithelial cell polarity.
, 百拇医药
Physiol Rev 1999;79:73-98
4 Citi S, Denisenko N. Phosphorylation of the tight junction proteincingulin and the effects of protein kinase inhibitors
and activators in MDCK epithelial cells. JCell Sci 1995;108(pt8):2917-2926
5 Tsukita S, Furuse M. Occludin and claudins in tight-junctionstrands:leading or supporting players?
Trends Cell Biol 1999;9:268-273
, 百拇医药
6 Morita K, Huruse M, Fujimoto K, Tsukita S. Claudin multigene familyencoding four-transmembrane domain protein
components of tight junction strands. ProcNatl Acad Sci USA 1999;96:511-516
7 Citi S, Sabanay H, Jakes R, Geiger B, Kendrick-Jones J. Cingulin, anew peripheral component of tight junctions.
Nature 1988;333:272-276
8 Keon BH, Schafer S, Kuhn C, Grund C, Franke WW. Symplekin, a noveltype of tight junction plaque protein.
, http://www.100md.com
J Cell Biol 1996;134:1003-1018
9 Zhong Y, Saitoh T, Minase T, Sawada N, Enomoto K, Mori M.Monoclonal antibody 7H6 reacts with a novel tight
junction-associated protein distinct fromZO-1, cingulin and ZO-2. J Cell Biol 1993;120:477-483
10 Weber E, Berta G, Tousson A, St John P, Green MW, Gopalokrishnan U,Jilling T, Sorscher EJ, Elton TS, Abrahamson
DR. Expression and polarizedtargeting of a rab3 isoform in epithelial cells. J Cell Biol 1994;125:583-594
, http://www.100md.com
11 Martin-Padura I, Lostaglio S, Schneemann M, Williams L, Romano M,Fruscella P, Panzeri C, Stoppacciaro A, Ruco L,Villa A, Simmons D, Dejana E.Junctional adhesion molecule, a novel member of the immunoglobulinsuperfamily that
distributes at intercellularjunctions and modulates monocyte transmigration. J Cell Biol 1998;142:117127
12 Madara JL. Intestinal absorptive cell tight junctions are linked tocytoskeleton. Am J Physiol 1987;253(1pt1):C171-C175
, 百拇医药
13 van Meer G, Simons K. The function of tight junctions inmaintaining differences in lipid composition between the
apical and the basolateral cellsurface domains of MDCK cells. EMBO J 1986;5:1455-1464
14 Hauser H, Howell K, Dawson RM, Bowyer DE. Rabbit small intestinalbrush border membrane preparation and lipid
composition. Biochim Biophys Acta 1980;602:567-577
, http://www.100md.com
15 Ebnet K, Aurrand-Lions M, Kuhn A, Kiefer F, Butz S, Zander K, Meyerzu Brickwedde MK, Suzuki A, Imhof BA,Vestweber D. The junctional adhesionmolecule (JAM) family members JAM-2 and JAM-3 associate with the cell
polarity protein PAR-3: a possiblerole for JAMs in endothelial cell polarity. J Cell Sci 2003;116(pt19):3879-3891
16 Hollander D, Vadheim CM, Brettholz E, Petersen GM, Delahunty T,Rotter J. Increased intestinal permeability in
, http://www.100md.com
patients with Crohn's disease andtheir relatives. Ann Intern Med 1986;105:883-885
17 Bjarnason I. Intestinal permeability. Gut 1994;35(1Suppl):S18-S22
18 Yamaguchi Y, Dalle-Molle E, Hardison WG. Vasopressin and A23187stimulate phosphorylation of myosin light chain-1
in isolated rat hepatocytes. Am JPhysiol 1991;261(2pt1):G312-G319
19 Behrens J, Vakaet L, Friis R, Winterhager E, Van Roy F, Mareel MM,Birchmeier W. Loss of epithelial differentiation
, 百拇医药
and gain of invasivenesscorrelates with tyrosine phosphorylation of the E-cadherin/beta-catenincomplex in
cells transformed with atemperature-sensitive v-SRC gene. J Cell Biol 1993;120:757 -766
20 Meyer TN, Hunt J, Schwesinger C, Denker BM. Ga12regulates epithelial cell junctions through Src tyrosine kinases.
Am J Physiol Cell Physiol 2003;285:C1281-C1293
, 百拇医药 21 Gopalakrishnan S, Raman N, Atkinson SJ, Marrs JA. Rho GTPasesignaling regulates tight junction assembly and
protects tight junctions during ATPdepletion. Am J Physiol 1998;275(3pt1):C798-C809
22 Hopkins AM, Walsh SV, Verkade P, Boquet P, Nusrat A. Constitutiveactivation of Rho proteins by CNF-1 influences
tight junction structure andepithelial barrier function. J Cell Sci 2003;116(pt4):725-742
, 百拇医药
23 Tavelin S, Hashimoto K, Malkinson J, Lazorova L, Toth I, ArturssonP. A new principle for tight junction modulation
based on occludin peptides. MolPharmacol 2003;64:1530-1540
24 Rao JN, Li L, Golovina VA, Platoshyn O, Strauch ED, Yuan J X, WangJY. Ca2+-RhoAsignaling pathway required
for polyamine-dependent intestinalepithelial cell migration. Am J Physiol Cell Physiol 2001;280:C993-C1007
, http://www.100md.com
25 Mankertz J, Hillenbrand B, Tavalali S, Huber O, Fromm M, SchulzkeJ. Functional crosstalk between Wnt signaling
and Cdx-related transcriptionalactivation in the regulation of the claudin-2 promoter activity.
Biochem Biophys Res Commun 2004;314:10011007
26 Abbott A. Microbiology:gut reaction. Nature 2004;427:284-286
27 Hirano J, Yoshida T, Sugiyama T, Koide N, Mori I, Yokochi T. Theeffect of Lactobacillus rhamnosus on
, 百拇医药
enterohemorrhagic Escherichia coliinfection of human intestinal cells in vitro.
Microbiol Immunol 2003;47:405-409
28 Berkes J, Viswanathan VK, Savkovic SD, Hecht G. Intestinalepithelial responses to enteric pathogens:effects on the
tight junction barrier, iontransport, and inflammation. Gut 2003;52:439-451
29 Resta-Lenert S, Barrett K E. Live probiotics protect intestinalepithelial cells from the effects of infection with
, 百拇医药
enteroinvasive Escherichia coli(EIEC).Gut 2003;52:988-997
30 Yan F, Polk DB. Probiotic bacterium prevents cytokine-inducedapoptosis in intestinal epithelial cells.
J Biol Chem 2002;277:50959-50965
31 Michail S, Abernathy F. Lactobacillus plantarum reduces the invitro secretory response of intestinal epithelial cells
to enteropathogenic Escherichia coliinfection. J Pediatr Gastroenterol Nutr 2002;35:350-355
编辑 张海宁, 百拇医药( 秦环龙, 高志光)
