Longitudinal cell formation in the entire human small intestine is correlated with the localization of Hath1 and Klf4

被引:13
作者
Iwasaki, Michiko [1 ]
Tsuchiya, Kiichiro [1 ]
Okamoto, Ryuichi [1 ,2 ]
Zheng, Xiu [1 ]
Kano, Yoshihito [1 ]
Okamoto, Eiko [1 ]
Okada, Eriko [1 ,4 ]
Araki, Akihiro [1 ,4 ]
Suzuki, Shinji [1 ]
Sakamoto, Naoya [1 ,3 ]
Kitagaki, Keisuke [5 ]
Akashi, Takumi [5 ]
Eishi, Yoshinobu [5 ]
Nakamura, Tetsuya [1 ,2 ]
Watanabe, Mamoru [1 ]
机构
[1] Tokyo Med & Dent Univ, Grad Sch, Dept Gastroenterol & Hepatol, Bunkyo Ku, Tokyo 1138519, Japan
[2] Tokyo Med & Dent Univ, Grad Sch, Dept Adv Therapeut Gastrointestinal Dis, Tokyo, Japan
[3] Tokyo Med & Dent Univ, Dept Hepatitis Control, Tokyo, Japan
[4] Tokyo Med & Dent Univ, Dept Endoscop Diag & Therapy, Tokyo, Japan
[5] Tokyo Med & Dent Univ, Grad Sch, Dept Pathol, Tokyo, Japan
关键词
Double balloon endoscopy; Goblet cells; Paneth cells; Hath1; Atoh1; WIRELESS CAPSULE ENDOSCOPY; ILEAL CROHNS-DISEASE; BETA-CATENIN; COLON-CANCER; DIFFERENTIATION; ENTEROSCOPY; GUT; REQUIREMENT; EXPRESSION; PEPTIDES;
D O I
10.1007/s00535-010-0346-x
中图分类号
R57 [消化系及腹部疾病];
学科分类号
100201 [内科学];
摘要
Double balloon endoscopy (DBE) enables the observation and collection of viable specimens from the entire intestine, thereby allowing more detailed investigation of how the structure and function of the human small intestine are regulated. The present study aimed to elucidate the regulation of cell formation in the human small intestine using biopsy specimens collected from an entire individual small intestine by DBE. The expression and the localization of representative genes for the differentiation program were analyzed in the entire small intestine of 10 patients. The functional correlation between Hath1 and Klf4 was analyzed in an intestinal cell line by using a Tet-On system. In longitudinal cell formation in the small intestine, it was shown that goblet cells, but not Paneth cells, increased toward the ileum in each individual small intestine. Immunohistochemistry showed that Hath1-expressing cells migrated from the base of the crypt to the top of the villi in the terminal ileum, while Klf4-expressing cells migrated from the top of the villus, resulting in the colocalization of Hath1 and Klf4 in the terminal ileum. Coexpression of Hath1 and Klf4 upregulated the expression of phenotypic genes for goblet cells following the downregulation of those for Paneth cells. Using mapping biopsy by DBE, we have demonstrated, for the first time, the molecular basis of the villus structure in the entire human small intestine in vivo. The present study showed that longitudinal cell formation was regulated by the colocalization of Hath1 and Klf4 that converted Paneth cell differentiation into goblet cell differentiation.
引用
收藏
页码:191 / 202
页数:12
相关论文
共 32 条
[1]
A randomized trial comparing wireless capsule endoscopy with push enteroscopy for the detection of small-bowel lesions [J].
Appleyard, M ;
Fireman, Z ;
Glukhovsky, A ;
Jacob, H ;
Shreiver, R ;
Kadirkamanathan, S ;
Lavy, A ;
Lewkowicz, S ;
Scapa, E ;
Shofti, R ;
Swain, P ;
Zaretsky, A .
GASTROENTEROLOGY, 2000, 119 (06) :1431-1438
[2]
Proteasomal degradation of Atoh1 by aberrant Wnt signaling maintains the undifferentiated state of colon cancer [J].
Aragaki, Mikayo ;
Tsuchiya, Kiichiro ;
Okamoto, Ryuichi ;
Yoshioka, Sanae ;
Nakamura, Tetsuya ;
Sakamoto, Naoya ;
Kanai, Takanorl ;
Watanabe, Mamoru .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2008, 368 (04) :923-929
[3]
Host-bacterial mutualism in the human intestine [J].
Bäckhed, F ;
Ley, RE ;
Sonnenburg, JL ;
Peterson, DA ;
Gordon, JI .
SCIENCE, 2005, 307 (5717) :1915-1920
[4]
The gut and energy balance: Visceral allies in the obesity wars [J].
Badman, MK ;
Flier, JS .
SCIENCE, 2005, 307 (5717) :1909-1914
[5]
CHUNG YC, 1979, GASTROENTEROLOGY, V76, P1415
[6]
Wnt/β-catenin signaling in development and disease [J].
Clevers, Hans .
CELL, 2006, 127 (03) :469-480
[7]
Organizing cell renewal in the intestine: stem cells, signals and combinatorial control [J].
Crosnier, C ;
Stamataki, D ;
Lewis, J .
NATURE REVIEWS GENETICS, 2006, 7 (05) :349-359
[8]
Trefoil peptide expression and goblet cell number in rat intestine:: effects of KGF and fasting-refeeding [J].
Fernández-Estívariz, C ;
Gu, LH ;
Gu, L ;
Jonas, CR ;
Wallace, TM ;
Pascal, RR ;
Devaney, KL ;
Farrell, CL ;
Jones, DP ;
Podolsky, DK ;
Ziegler, TR .
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 2003, 284 (02) :R564-R573
[9]
Notch signals control the fate of immature progenitor cells in the intestine [J].
Fre, S ;
Huyghe, M ;
Mourikis, P ;
Robine, S ;
Louvard, D ;
Artavanis-Tsakonas, S .
NATURE, 2005, 435 (7044) :964-968
[10]
In vivo gene expression profiling of human intestinal epithelial cells:: analysis by laser microdissection of formalin fixed tissues [J].
George, Michael D. ;
Wehkamp, Jan ;
Kays, Robert J. ;
Leutenegger, Christian M. ;
Sabir, Sadiah ;
Grishina, Irina ;
Dandekar, Satya ;
Bevins, Charles L. .
BMC GENOMICS, 2008, 9 (1)