Mechanisms and modulation of intestinal epithelial repair

被引:200
作者
Dignass, AU [1 ]
机构
[1] Charite, Virchow Clin, Dept Med, Div Gastroenterol & Hepatol, D-13353 Berlin, Germany
关键词
growth factor; regulatory peptide; cytokine; wound healing; repair; restitution; proliferation; lysophosphatidic acid;
D O I
10.1097/00054725-200102000-00014
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
The mucosal epithelium of the alimentary tract represents a crucial barrier to a broad spectrum of noxious and immunogenic substances within the intestinal lumen. An impairment of the integrity of the mucosal epithelial barrier is observed in the course of various intestinal disorders including inflammatory bowel diseases (IBD), celiac disease, intestinal infections, and various other diseases. Furthermore, even under physiologic conditions temporary damage of the epithelial surface mucosa may be caused by proteases, residential flora, dietary compounds, or other factors. Generally, the integrity of the intestinal mucosal surface barrier is rapidly reestablished even after extensive destruction because of an enormous regenerative capability of the mucosal surface epithelium. Rapid resealing of the surface epithelium is accomplished by epithelial cell migration, also termed epithelial restitution, epithelial cell proliferation, and differentiation. Healing of the intestinal surface epithelium is regulated by a complex network of highly divergent factors, among them a broad spectrum of structurally distinct regulatory peptides that have been identified within the mucosa of the intestinal tract. These regulatory peptides, conventionally designated as growth factors and cytokines, play an essential role in regulating differential epithelial cell functions to preserve normal homeostasis and integrity of the intestinal mucosa. In addition, a number of other peptide molecules such as extracellular matrix factors and blood clotting factors, and also nonpeptide molecules including phospholipids, short-chain fatty acids, adenine nucleotides, trace elements, and pharmacological agents, have been demonstrated to modulate intestinal epithelial repair mechanisms. Some of these molecules may be released by platelets, adjacent stromal cells, inflammatory cells, or injured epithelial and nonepithelial cells and may play an important role in the modulation of intestinal injury. Repeated damage and injury of the intestinal surface are key features of various intestinal disorders including IBD and require constant repair of the epithelium. Enhancement of intestinal repair mechanisms by regulatory peptides or other modulatory factors may provide future approaches for the treatment of diseases that are characterized by injuries of the epithelial surface.
引用
收藏
页码:68 / 77
页数:10
相关论文
共 121 条
[1]   EXPRESSION OF GROWTH-FACTOR RECEPTOR-ENCODED MESSENGER-RNA BY COLONIC EPITHELIAL-CELLS IS ALTERED IN INFLAMMATORY BOWEL-DISEASE [J].
ALEXANDER, RJ ;
PANJA, A ;
KAPLANLISS, E ;
MAYER, L ;
RAICHT, RF .
DIGESTIVE DISEASES AND SCIENCES, 1995, 40 (03) :485-494
[2]   THE ROLE OF GROWTH-FACTORS IN GASTROINTESTINAL CELL-PROLIFERATION [J].
ALISON, MR ;
SARRAF, CE .
CELL BIOLOGY INTERNATIONAL, 1994, 18 (01) :1-10
[3]  
Babyatsky M. W., 1991, TXB GASTROENTEROLOGY, P475
[4]   Oral trefoil peptides protect against ethanol- and indomethacin-induced gastric injury in rats [J].
Babyatsky, MW ;
deBeaumont, M ;
Thim, L ;
Podolsky, DK .
GASTROENTEROLOGY, 1996, 110 (02) :489-497
[5]   Expression of transforming growth factors alpha and beta in colonic mucosa in inflammatory bowel disease [J].
Babyatsky, MW ;
Rossiter, G ;
Podolsky, DK .
GASTROENTEROLOGY, 1996, 110 (04) :975-984
[6]  
BajajElliott M, 1997, AM J PATHOL, V151, P1469
[7]   GUT HORMONES, GROWTH AND MALIGNANCY [J].
BALDWIN, GS ;
WHITEHEAD, RH .
BAILLIERES CLINICAL ENDOCRINOLOGY AND METABOLISM, 1994, 8 (01) :185-214
[8]   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
[9]   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
[10]  
BASSON MD, 1992, SURGERY, V112, P299