三叶因子家族研究进展
卢雅丕,任建林,厦门大学医学院第一临床学院消化内科福建省厦门市 361004
项目负责人:任建林,361004, 福建省厦门市,厦门大学医学院第一临床学院消化内科. jianlinr@msn.com
电话:0592-2292017 传真:0592-2292017
收稿日期:2003-08-13 接受日期:2003-10-07
摘要三叶因子家族(trefoilfactor family，TFF)是一群主要由胃肠道黏液细胞分泌的小分子多肽.其共同特征为均含一特殊的P结构域，由38-39个氨基酸通过6个半胱氨酸残基经由3个二硫键相互联接，使整个肽链扭曲、折叠形成三叶状结构，由此命名.这种结构的稳定性使三叶因子家族具有明显的抗蛋白酶水解、酸消化及耐热特性，因而能在消化道复杂的环境中保持生物活性.目前在哺乳动物体内发现的有pS2/TFF1、SP/TFF2和ITF/TFF3三种，他们具有黏膜保护与修复、肿瘤抑制、信号传导、调节细胞凋亡等功能.
, 百拇医药
卢雅丕,任建林. 三叶因子家族研究进展.世界华人消化杂志 2003;11(12):2019-2021
Pera M, Heppell J, Poulsom R, Teixeira FV, Williams J. Ulcerassociated cell lineage glands expressing trefoil peptide
genes are induced by chronic ulceration inileal pouch mucosa. Gut 2001;48:792-796
4 Masiakowski P, Breathnach R, Bloch J, Gannon F, Krust A, Chambon P.Cloning of cDNA sequences of hormone-regulated
, 百拇医药
genes from the MCF-7 human breast cancercell line. Nucl Acids Res 1982;10:7895-7903
5 Chadwick MP, Westley BR, May FE. Homodimerization and hetero-oligomerizationof the single-domain trefoil protein
pNR-2/pS2 through cysteine 58. Biochem J 1997;327(Pt 1):117123
6 Jorgensen KH, Thim L, Jacobsen HE. Pancreatic spasmolyticpolypeptide (PSP). I. Preparation and initial chemical
, http://www.100md.com
characterization of a new polypeptide fromporcine pancreas. Regul Pept 1982;3:207-219
7 Semple JI, Newton JL, Westley BR, May FE. Dramatic diurnalvariation in the concentration of the human trefoil peptide
TFF2 in gastric juice. Gut 2001;48:648655
8 Suemori S, Lynch-Devaney K, Podolsky DK. Identification andcharacterization of rat intestinal trefoil factor: tissue-and
, http://www.100md.com
cell-specific member of the trefoil proteinfamily. Proc Natl Acad Sci USA 1991;88:11017-11021
9 Thim L, Woldike HF, Nielsen PF, Christensen M, Lynch-Devaney K,Podolsky DK. Characterization of human and rat
intestinal trefoil factor produced inyeast. Biochemistry 1995;34:4757-4764
10 Polshakov VI, Williams MA, Gargaro AR, Frenkiel TA, West ChadwickMP, May FE, Feeney J. High-resolution solution
, http://www.100md.com
structure of human pNR-2/pS2: a singletrefoil motif protein. J Mol Biol 1997;267:418-432
11 Playford RJ, Marchbank T, Chinery R, Evison R, Pignatelli M,Boulton RA, Thim L, Hanby AM. Human spasmolytic
polypeptide is a cytoprotective agent thatstimulates cell migration. Gastroenterology 1995;108:108116
12 Poulsen SS, Thulesen J, Nex E, Thim L. Distribution and metabolismof intravenously administered trefoil factor
, 百拇医药
2/porcine spasmolytic polypeptide in therat.Gut 1998;43:240247
13 Thim L, Mortz E. Isolation and characterization of putative trefoilpeptide receptors. Regul Pept 2000;90:6168
14 Newton JL, Allen A, Westley BR, May FE. The human trefoil peptide,TFF1, is present in different molecular forms that
are intimately associated with mucus innormal stomach. Gut 2000;46:312-320
, 百拇医药
15 Babyatsky M, de Beaumont M, Thim L, Podolsky DK. Oral trefoilpeptides protect against ethanol and indomethacin-
induced gastric injury in rats.Gastroenterology 1996;110:489-497
16 Poulsen SS, Thulesen J, Christensen L, Nexo E, Thim L. Metabolismof oral trefoil factor2(TFF2) and the effect of oral
and parenteral TFF2 on gastric and duodenalulcer healing in the rat. Gut 1999;45:516-522
, http://www.100md.com
17 Wong WM, Poulsom R, Wright NA. Trefoil peptides. Gut1999;44:890-895
18 Longman RJ, Douthwaite J, Sylvester PA, Poulsom R, Corfield AP,Thomas MG, Wright NA. Coordinated localization of
mucins and trefoil peptides in the ulcerassociated cell lineage and the gastrointestinal mucosa. Gut 2000;47:792-800
19 Dignass A, Lynch-Devaney K, Kindon H, Thim L, Podolsky DK. Trefoilpeptides promote epithelial migration through a
, 百拇医药
transforming growth factor-bindependent pathway. J Clin Invest 1994;94:376-383
20 Oertel M, Graness A, Thim L, Buhling F, Kalbacher H, Hoffmann W.Trefoil factor family-peptides promote migration
of human bronchial epithelial cells:synergistic effect with epidermal growth factor. Am J Respir Cell Mol Biol
2001;25:418-424
21 Lefebvre O, Chenard MP, Masson R, Linares J, Dierich A, LeMeur M,Wendling C, Tomasetto C, Chambon P, Rio MC.
, 百拇医药
Gastric mucosa abnormalities andtumorigenesis in mice lacking the pS2 trefoil protein. Science 1996;274:259-262
22 Tomasetto C, Wolf C, Rio MC, Mehtali M, LeMeur M, Gerlinger P,Chambon P, Lathe R. Breast cancer protein pS2
synthesis in mammary gland of transgenicmice and secretion into milk.Mol Endocrinol 1989;3:1579-1584
23 Yamachika T, Werther JL, Bodian C, Babyatsky M, Tatematsu M,Yamamura Y, Chen A, Itzkowitz S. Intestinal trefoil
, 百拇医药
factor: a marker of poor prognosis ingastric carcinoma. Clin Cancer Res 2002;8:1092-1099
24 Kanai M, Mullen C, Podolsky DK. Intestinal trefoil factor inducesinactivation of extracellular signal-regulated protein
kinase in intestinal epithelial cells. ProcNatl Acad Sci USA 1998;95:178-182
25 Efstathiou JA, Noda M, Rowan A, Dixon C, Chinery R, Jawhari A,Hattori T, Wright NA, Bodmer WF, Pignatelli M.
, http://www.100md.com
Intestinal trefoil factor controls theexpression of the adenomatous polyposis coli-catenin and the E-cadherin-catenin
complexes in human colon carcinoma cells.Proc Natl Acad Sci USA 1998;95:3122-3127
26 Bossenmeyer-Pourie C, Kannan R, Ribieras S, Wendling C, Stoll I,Thim L, Tomasetto C, Rio MC. The trefoil factor
1 participates in gastrointestinal celldifferentiation by delaying G1-S phase transition and reducing apoptosis.J
, http://www.100md.com
Cell Biol 2002; 157:761-770
27 Farrell JJ, Taupin D, Koh TJ, Chen D, Zhao CM, Podolsky TC.TFF2/SP-deficient mice show decreased gastric
proliferation, increased acid secretion,and increased susceptibility to NSAID injury. J Clin Invest 2002;109:193-204
28 口如琴,王蔚, 李令媛,茹炳根. 小肠三叶因子对盐酸诱导的大鼠胃溃疡的预防与治疗作用.中国药理学通报
2000;16:178-181
29 Cook GA, Thim L, Yeomans ND, Giraud AS. Oral human spasmolyticpolypeptide protects against aspirin-induced gastric
injury in rats. J Gastroenterol Hepatol1998;13:363-370, http://www.100md.com( 卢雅丕 , 任建林)
项目负责人:任建林,361004, 福建省厦门市,厦门大学医学院第一临床学院消化内科. jianlinr@msn.com
电话:0592-2292017 传真:0592-2292017
收稿日期:2003-08-13 接受日期:2003-10-07
摘要三叶因子家族(trefoilfactor family，TFF)是一群主要由胃肠道黏液细胞分泌的小分子多肽.其共同特征为均含一特殊的P结构域，由38-39个氨基酸通过6个半胱氨酸残基经由3个二硫键相互联接，使整个肽链扭曲、折叠形成三叶状结构，由此命名.这种结构的稳定性使三叶因子家族具有明显的抗蛋白酶水解、酸消化及耐热特性，因而能在消化道复杂的环境中保持生物活性.目前在哺乳动物体内发现的有pS2/TFF1、SP/TFF2和ITF/TFF3三种，他们具有黏膜保护与修复、肿瘤抑制、信号传导、调节细胞凋亡等功能.
, 百拇医药
卢雅丕,任建林. 三叶因子家族研究进展.世界华人消化杂志 2003;11(12):2019-2021
Pera M, Heppell J, Poulsom R, Teixeira FV, Williams J. Ulcerassociated cell lineage glands expressing trefoil peptide
genes are induced by chronic ulceration inileal pouch mucosa. Gut 2001;48:792-796
4 Masiakowski P, Breathnach R, Bloch J, Gannon F, Krust A, Chambon P.Cloning of cDNA sequences of hormone-regulated
, 百拇医药
genes from the MCF-7 human breast cancercell line. Nucl Acids Res 1982;10:7895-7903
5 Chadwick MP, Westley BR, May FE. Homodimerization and hetero-oligomerizationof the single-domain trefoil protein
pNR-2/pS2 through cysteine 58. Biochem J 1997;327(Pt 1):117123
6 Jorgensen KH, Thim L, Jacobsen HE. Pancreatic spasmolyticpolypeptide (PSP). I. Preparation and initial chemical
, http://www.100md.com
characterization of a new polypeptide fromporcine pancreas. Regul Pept 1982;3:207-219
7 Semple JI, Newton JL, Westley BR, May FE. Dramatic diurnalvariation in the concentration of the human trefoil peptide
TFF2 in gastric juice. Gut 2001;48:648655
8 Suemori S, Lynch-Devaney K, Podolsky DK. Identification andcharacterization of rat intestinal trefoil factor: tissue-and
, http://www.100md.com
cell-specific member of the trefoil proteinfamily. Proc Natl Acad Sci USA 1991;88:11017-11021
9 Thim L, Woldike HF, Nielsen PF, Christensen M, Lynch-Devaney K,Podolsky DK. Characterization of human and rat
intestinal trefoil factor produced inyeast. Biochemistry 1995;34:4757-4764
10 Polshakov VI, Williams MA, Gargaro AR, Frenkiel TA, West ChadwickMP, May FE, Feeney J. High-resolution solution
, http://www.100md.com
structure of human pNR-2/pS2: a singletrefoil motif protein. J Mol Biol 1997;267:418-432
11 Playford RJ, Marchbank T, Chinery R, Evison R, Pignatelli M,Boulton RA, Thim L, Hanby AM. Human spasmolytic
polypeptide is a cytoprotective agent thatstimulates cell migration. Gastroenterology 1995;108:108116
12 Poulsen SS, Thulesen J, Nex E, Thim L. Distribution and metabolismof intravenously administered trefoil factor
, 百拇医药
2/porcine spasmolytic polypeptide in therat.Gut 1998;43:240247
13 Thim L, Mortz E. Isolation and characterization of putative trefoilpeptide receptors. Regul Pept 2000;90:6168
14 Newton JL, Allen A, Westley BR, May FE. The human trefoil peptide,TFF1, is present in different molecular forms that
are intimately associated with mucus innormal stomach. Gut 2000;46:312-320
, 百拇医药
15 Babyatsky M, de Beaumont M, Thim L, Podolsky DK. Oral trefoilpeptides protect against ethanol and indomethacin-
induced gastric injury in rats.Gastroenterology 1996;110:489-497
16 Poulsen SS, Thulesen J, Christensen L, Nexo E, Thim L. Metabolismof oral trefoil factor2(TFF2) and the effect of oral
and parenteral TFF2 on gastric and duodenalulcer healing in the rat. Gut 1999;45:516-522
, http://www.100md.com
17 Wong WM, Poulsom R, Wright NA. Trefoil peptides. Gut1999;44:890-895
18 Longman RJ, Douthwaite J, Sylvester PA, Poulsom R, Corfield AP,Thomas MG, Wright NA. Coordinated localization of
mucins and trefoil peptides in the ulcerassociated cell lineage and the gastrointestinal mucosa. Gut 2000;47:792-800
19 Dignass A, Lynch-Devaney K, Kindon H, Thim L, Podolsky DK. Trefoilpeptides promote epithelial migration through a
, 百拇医药
transforming growth factor-bindependent pathway. J Clin Invest 1994;94:376-383
20 Oertel M, Graness A, Thim L, Buhling F, Kalbacher H, Hoffmann W.Trefoil factor family-peptides promote migration
of human bronchial epithelial cells:synergistic effect with epidermal growth factor. Am J Respir Cell Mol Biol
2001;25:418-424
21 Lefebvre O, Chenard MP, Masson R, Linares J, Dierich A, LeMeur M,Wendling C, Tomasetto C, Chambon P, Rio MC.
, 百拇医药
Gastric mucosa abnormalities andtumorigenesis in mice lacking the pS2 trefoil protein. Science 1996;274:259-262
22 Tomasetto C, Wolf C, Rio MC, Mehtali M, LeMeur M, Gerlinger P,Chambon P, Lathe R. Breast cancer protein pS2
synthesis in mammary gland of transgenicmice and secretion into milk.Mol Endocrinol 1989;3:1579-1584
23 Yamachika T, Werther JL, Bodian C, Babyatsky M, Tatematsu M,Yamamura Y, Chen A, Itzkowitz S. Intestinal trefoil
, 百拇医药
factor: a marker of poor prognosis ingastric carcinoma. Clin Cancer Res 2002;8:1092-1099
24 Kanai M, Mullen C, Podolsky DK. Intestinal trefoil factor inducesinactivation of extracellular signal-regulated protein
kinase in intestinal epithelial cells. ProcNatl Acad Sci USA 1998;95:178-182
25 Efstathiou JA, Noda M, Rowan A, Dixon C, Chinery R, Jawhari A,Hattori T, Wright NA, Bodmer WF, Pignatelli M.
, http://www.100md.com
Intestinal trefoil factor controls theexpression of the adenomatous polyposis coli-catenin and the E-cadherin-catenin
complexes in human colon carcinoma cells.Proc Natl Acad Sci USA 1998;95:3122-3127
26 Bossenmeyer-Pourie C, Kannan R, Ribieras S, Wendling C, Stoll I,Thim L, Tomasetto C, Rio MC. The trefoil factor
1 participates in gastrointestinal celldifferentiation by delaying G1-S phase transition and reducing apoptosis.J
, http://www.100md.com
Cell Biol 2002; 157:761-770
27 Farrell JJ, Taupin D, Koh TJ, Chen D, Zhao CM, Podolsky TC.TFF2/SP-deficient mice show decreased gastric
proliferation, increased acid secretion,and increased susceptibility to NSAID injury. J Clin Invest 2002;109:193-204
28 口如琴,王蔚, 李令媛,茹炳根. 小肠三叶因子对盐酸诱导的大鼠胃溃疡的预防与治疗作用.中国药理学通报
2000;16:178-181
29 Cook GA, Thim L, Yeomans ND, Giraud AS. Oral human spasmolyticpolypeptide protects against aspirin-induced gastric
injury in rats. J Gastroenterol Hepatol1998;13:363-370, http://www.100md.com( 卢雅丕 , 任建林)
