The role of transforming growth factor beta-2, beta-3 in mediating apoptosis in the murine intestinal mucosa

被引:47
作者
Dünker, N [1 ]
Schmitt, K [1 ]
Schuster, N [1 ]
Krieglstein, K [1 ]
机构
[1] Univ Saarland, D-6650 Homburg, Germany
关键词
D O I
10.1053/gast.2002.32991
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & Aims: Apoptosis is especially relevant in the gastrointestinal tract because the mammalian intestinal mucosa undergoes continual epithelial regeneration. Most recently, we confirmed the proapoptotic role of endogenous transforming growth factor (TGF)-beta in the developing chick retina as well as in chick ciliary, dorsal root, and spinal motor neurons. In the present study, we determined to establish the role of TGF-beta2 and TGF-beta3 in mediating apoptosis in non-neuronal tissue by analyzing the intestinal mucosa of Tgfbeta2(+/-) and Tgfbeta3(+/-) heterozygous mice. Methods: Intestinal localization of TGF-beta2 and TGF-beta3 isoforms and antiapoptotic molecules Bcl-xL and Bcl-2 was examined immunocytochemically and by Western blot analysis. Apoptosis was detected by enzyme-linked immunosorbent assay and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling, and proliferation was detected by proliferating cell nuclear antigen stains. Results: TGF-beta2 was detected in endocrine cells, whereas TGF-beta3 was predominantly found in goblet cells. Programmed cell death was significantly reduced in the intestinal mucosa of Tgfbeta2(+/-) and Tgfbeta3(+/-) heterozygous mice. This decrease in apoptosis was accompanied by an increase in villus length; proliferation, however, seemed to remain unchanged. The level of Bcl-xL and Bcl-2 was significantly up-regulated in Tgfbeta2(+/-) and Tgfbeta3(+/-) mice. Conclusions: Our data show that TGF-beta2 and TGF-beta3 play an important role in mediating apoptosis in the intestinal mucosa and regulating apoptosis-associated proteins Bcl-xL and Bcl-2 in vivo.
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页码:1364 / 1375
页数:12
相关论文
共 43 条
[1]   Colocalization of BAX and BCL-2 in small intestine and kidney biopsies with different degrees of DNA fragmentation [J].
Aschoff, AP ;
Ott, U ;
Fünfstück, R ;
Stein, G ;
Jirikowski, GF .
CELL AND TISSUE RESEARCH, 1999, 296 (02) :351-357
[2]   TGF-BETA EXPRESSION IN THE HUMAN COLON - DIFFERENTIAL IMMUNOSTAINING ALONG CRYPT EPITHELIUM [J].
AVERY, A ;
PARASKEVA, C ;
HALL, P ;
FLANDERS, KC ;
SPORN, M ;
MOORGHEN, M .
BRITISH JOURNAL OF CANCER, 1993, 68 (01) :137-139
[3]   LOCALIZATION OF TRANSFORMING GROWTH-FACTOR-BETA ISOFORMS IN THE NORMAL MURINE SMALL-INTESTINE AND COLON [J].
BARNARD, JA ;
WARWICK, GJ ;
GOLD, LI .
GASTROENTEROLOGY, 1993, 105 (01) :67-73
[4]   REGULATION OF INTESTINAL EPITHELIAL-CELL GROWTH BY TRANSFORMING GROWTH-FACTOR TYPE-BETA [J].
BARNARD, JA ;
BEAUCHAMP, RD ;
COFFEY, RJ ;
MOSES, HL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (05) :1578-1582
[5]   QUANTITATIVE STUDY OF APOPTOSIS IN NORMAL RAT GASTRODUODENAL MUCOSA [J].
BENEDETTI, A ;
MANCINI, R ;
MARUCCI, L ;
PAOLUCCI, F ;
JEZEQUEL, AM ;
ORLANDI, F .
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 1990, 5 (04) :369-374
[6]  
CREAMER B, 1961, GUT, P117
[7]   Smad4 (DPC4) - a potent tumour suppressor? [J].
Duff, EK ;
Clarke, AR .
BRITISH JOURNAL OF CANCER, 1998, 78 (12) :1615-1619
[8]  
Dünker N, 2001, DEVELOPMENT, V128, P1933
[9]   Targeted mutations of transforming growth factor-β genes reveal important roles in mouse development and adult homeostasis [J].
Dünker, N ;
Krieglstein, K .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 2000, 267 (24) :6982-6988
[10]  
Engle SJ, 1999, CANCER RES, V59, P3379