Mitogenic influence of human R-spondin1 on the intestinal epithelium

被引：462

作者：

Kim, KA

Kakitani, M

Zhao, JS

Oshima, T

Tang, T

Binnerts, M

Liu, Y

Boyle, B

Park, E

Emtage, P

Funk, WD

Tomizuka, K

机构：

[1] Nuvelo Inc, Sunnyvale, CA 94085 USA

[2] Kirin Brewery Co Ltd, Div Pharmaceut, Pharmaceut Res Labs, Takasaki, Gumma 3701295, Japan

来源：

SCIENCE | 2005年 / 309卷 / 5738期

关键词：

D O I：

10.1126/science.1112521

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Several described growth factors influence the proliferation and regeneration of the intestinal epithelium. Using a transgenic mouse model, we identified a human gene, R-spondin1, with potent and specific proliferative effects on intestinal crypt cells. Human R-spondin1 (hRSpo1) is a thrombospondin domain-containing protein expressed in enteroendocrine cells as well, as in epithelial cells in various tissues. Upon injection into mice, the protein induced rapid onset of crypt cell proliferation involving beta-catenin stabilization, possibly by a process that is distinct from the canonical Wnt-mediated signaling pathway. The protein also displayed efficacy in a model of chemotherapy-induced intestinal mucositis and may have therapeutic application in gastrointestinal diseases.

引用

页码：1256 / 1259

页数：4

共 22 条

[1] β-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/EphrinB [J].

Batlle, E ;

Henderson, JT ;

Beghtel, H ;

van den Born, MMW ;

Sancho, E ;

Huls, G ;

Meeldijk, J ;

Robertson, J ;

van de Wetering, M ;

Pawson, T ;

Clevers, H .

CELL, 2002, 111 (02) :251-263

[2] Transforming growth factor-β mediates intestinal healing and susceptibility to injury in vitro and in vivo through epithelial cells [J].

Beck, PL ;

Rosenberg, IM ;

Xavier, RJ ;

Koh, T ;

Wong, JF ;

Podolsky, DK .

AMERICAN JOURNAL OF PATHOLOGY, 2003, 162 (02) :597-608

[3] Linking colorectal cancer to Wnt signaling [J].

Bienz, M ;

Clevers, H .

CELL, 2000, 103 (02) :311-320

[4] Modulation of specific intestinal epithelial progenitors by enteric neurons [J].

Bjerknes, M ;

Cheng, H .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (22) :12497-12502

[5]

Boushey RP, 2001, CANCER RES, V61, P687

[6]

Farrell CL, 1998, CANCER RES, V58, P933

[7] Caught up in a Wnt storm: Wnt signaling in cancer [J].

Giles, RH ;

van Es, JH ;

Clevers, H .

BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2003, 1653 (01) :1-24

[8] KERATINOCYTE GROWTH-FACTOR INDUCES PROLIFERATION OF HEPATOCYTES AND EPITHELIAL-CELLS THROUGHOUT THE RAT GASTROINTESTINAL-TRACT [J].

HOUSLEY, RM ;

MORRIS, CF ;

BOYLE, W ;

RING, B ;

BILTZ, R ;

TARPLEY, JE ;

AUKERMAN, SL ;

DEVINE, PL ;

WHITEHEAD, RH ;

PIERCE, GF .

JOURNAL OF CLINICAL INVESTIGATION, 1994, 94 (05) :1764-1777

[9] Wnt/β-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway [J].

Jho, EH ;

Zhang, T ;

Domon, C ;

Joo, CK ;

Freund, JN ;

Costantini, F .

MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (04) :1172-1183

[10] A novel transgenic chimaeric mouse system for the rapid functional evaluation of genes encoding secreted proteins [J].

Kakitani, M ;

Oshima, T ;

Horikoshi, K ;

Yoshitome, T ;

Ueda, A ;

Kajikawa, M ;

Iba, Y ;

Ozone, Y ;

Ijima, Y ;

Yoshino, T ;

Itoh, M ;

Seki, S ;

Aoki, A ;

Ishihara, T ;

Shionoya, M ;

Makino, U ;

Kitada, R ;

Ohguma, A ;

Ohta, T ;

Yoshida, Y ;

Kudoh, H ;

Hanaoka, K ;

Sibuya, K ;

Ishida, I ;

Kakeda, M ;

Yagi, M ;

Yoneya, T ;

Tomizuka, K .

NUCLEIC ACIDS RESEARCH, 2005, 33 (09) :1-8

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