Table of Contents

Intestinal architecture and development.
Mucosal wall architecture.
Development and functions.
Small intestine.
Large intestine.
Characteristics of gut mucosal growth.
Intestinal stem cells.
ISCs and their niches.
Signaling pathways regulating ISCs.
Wnt signaling pathway.
BMP pathway.
Notch pathway.
Role of GI hormones on the gut mucosal growth.
Bombesin/gastrin-releasing peptide.
Other GI hormones.
Peptide growth factors in GI mucosal growth.
EGF family.
TGF-b family.
IGF family.
FGF family.
Other factors.
Luminal nutrients and microbes in gut mucosal growth.
Luminal factors.
Microbes in health and mucosal growth.
Dietary supplements.
Polyamines in the regulation of mucosal growth.
Polyamine metabolism.
Polyamines stimulate mucosal growth by enhancing gene transcription.
Polyamines regulate epithelial renewal by altering expression of protooncogenes.
Polyamines are required for protooncogene transcription.
Possible mechanisms of action of the polyamines.
Induced mRNA stabilization and growth arrest after polyamine depletion.
Polyamine depletion stabilizes p53.
Polyamines modulate JunD mRNA stability.
Polyamine depletion stabilizes TGF-b mRNA and activates Smad signaling.
Polyamines regulate apoptosis by altering the stability of ATF-2 and XIAP mRNAs.
Polyamines modulate the stability of mRNAs via the RNA-binding protein HuR.
Polyamines modulate subcellular trafficking of HuR.
Induced cytoplasmic HuR binds to target mRNAs in polyamine-deficient cells.
Induced HuR stabilizes its target mRNAs in polyamine-deficient cells.
mRNA translation by polyamines.
Summary and conclusions.
Author biographies. The mammalian gastrointestinal mucosa is a rapidly self-renewing tissue in the body, and its homeostasis is preserved through the strict regulation of epithelial cell proliferation, growth arrest, and apoptosis. The control of the growth of gastrointestinal mucosa is unique and, compared with most other tissue in the body, complex. Mucosal growth is regulated by the same hormones that alter metabolism in other tissues, but the gastrointestinal mucosa also responds to a host of events triggered by the ingestion and presence of food within the digestive tract. These gut hormones and peptides regulate the growth of the exocrine pancreas, gallbladder epithelium, and the mucosa of the oxyntic gland region of the stomach and the small and large intestines. Luminal factors (nutrients or other dietary factors, secretions, and microbes), which occur within the lumen and distribute over a proximal-to-distal gradient, are also crucial for the maintenance of the normal gut mucosal growth and could explain the villous height-crypt depth gradient and variety of adaptations since these factors are diluted, absorbed, and destroyed as they pass down the digestive tract. Recently, intestinal stem cells and polyamines are shown to play an important role in the regulation of gastrointestinal mucosal growth under physiological and various pathological conditions. In this chapter, we highlight key issues and factors that control gastrointestinal mucosal growth, with special emphasis on the mechanisms through which epithelial renewal is regulated by polyamines at the cellular and molecular levels.