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Rao JN, Wang JY. Regulation of Gastrointestinal Mucosal Growth. San Rafael (CA): Morgan & Claypool Life Sciences; 2010.

Cover of Regulation of Gastrointestinal Mucosal Growth

Regulation of Gastrointestinal Mucosal Growth.

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Characteristics of Gut Mucosal Growth

The gastrointestinal epithelium is a complex system that consists of multiple cell types undergoing continual renewal while maintaining precise interrelationships [2328]. Under biological conditions, a huge number of cells are exfoliated regularly throughout the lumen of the GI tract, and these sloughed cells are almost immediately replaced by new cells from the stem cell compartment. These stem cells or proliferative progenitors in the crypts generate epithelial cells that differentiate during their migration toward the villous region. A wide variety of dietary and growth factors and hormonal and transcriptional factors are involved in the regulation of GI mucosal growth and development [24,25,28]. A well-controlled cascade of signals maintains mucosal growth by the shedding of senescent and apoptotic cells at the surface of the GI epithelium [26,28,29]. The overall mucosal integrity depends on the dynamic balance between cell production and cell loss. A defect in cell production leads to the development of mucosal atrophy and results in a decrease in absorption, whereas mucosal hyperplasia results from excess production of newborn cells. Hyperplasia can cause hypersecretion and increase the risk of cancers [10,27,29].

The mucous neck cells are located throughout the stomach, predominantly in the upper portion (neck or isthmus) of each gland, immediately below the glandular junction [2,27] and are considered as gastric epithelial progenitor cells. In each gland, the mucous neck cells form the zone of epithelial cell renewal, giving rise to new surface faveolar mucous cells as well as the other cell types within the glands. It has been thought by many investigators for years that parietal (oxyntic) cells are unable to divide [30] and are replaced by newly formed cells migrating slowly down the gland and differentiating into acid-producing cells [31]. Based on the results obtained from cultured human gastric corpuses from 12 to 17 weeks of gestation, the proliferative compartment of the mucosa from which the differentiated cells arise is the neck portion at the base of the glandular compartments [2,6]. Most parietal cells occupy the mid portion of the gastric glands and are important in the processes of differentiation and development of the stomach. In the mouse, parietal cells survive for ∼90 days, which is the time period for migration to the bottom of the gland [27,32]. Another type of cells located in the gastric glands is zymogen (chief) cells which are concentrated at the base of the gastric glands. After injury, zymogen cells are derived from the stem cells, but they are replaced by the process of mitosis under normal circumstances [27,30]. In addition, several specialized endocrine-secreting cells are scattered in the antral region of the stomach. G-cells in this region produce gastrin. The levels of antral gastrin are varied during development, nutritional intake, and various disease states [33]. Regulation of G-cell populations is important because they participate in the GI mucosal growth through the release of gastrin that induces the growth of the oxyntic mucosa. In this regard, transgenic mice overexpressing gastrin exhibit an increased cell proliferation. In contrast, mice with a targeted deletion of gastrin display a decreased number of mature parietal cells with an increase in the number of mucous neck cells [34]. [3H]-thymidine incorporation studies have revealed that G-cells are derived by the mitosis cell division from other G cells [35], whereas gastrin infusion stimulates cell proliferation in the neck region of the oxyntic gland where gastric stem cells may reside. It is likely that gastrin interacts with gastric stem cells to stimulate their proliferation and differentiation into parietal cells.

The proliferative compartment of the small intestinal epithelium is structured as several bottle-shaped invaginations known as crypts of Lieberkuhn. Each of the intestinal crypts is a developmental unit that contributes to the renewal of the intestinal epithelium when growth progresses to adulthood. The crypts contain the crypt base columnar cells (CBC), believed to be intestinal stem cells (as discussed separately in another chapter), and slowly duplicate and eventually produce transient population of progenitor cells. The majority of epithelial cells migrates upward to the top of the villi and differentiates into endocrine, goblet cells, and enterocytes. Enterocytes responsible for the secretory and absorptive functions of the gut epithelium are the most abundant. The population of mucous producing goblet cells and endocrine cells makes up ∼5% and ∼1% of the total epithelial cells [2,6]. This process occurs continuously, cells are replaced at the tip of the villous every 4 to 5 days. This phenomenon in neonatal piglets, which enhances mitosis, is paralleled with a decrease in apoptosis at the first 2 days after birth, resulting in transient elevation of the mitosis/apoptosis ratio, which contributes to the enlargement of the gut mucosa [19]. GI mucosal cell growth is regulated by a number of nutritional and hormonal factors. For example, deprivation of food results in decreased cell proliferation, which is reversed by refeeding [13,26,28]. An interesting study has shown that ectopic expression of Cdx2 gene induces intestinal epithelial cell differentiation [36,37]. Several signaling pathways are shown to play an important role in patterning the gut during development and in regulating epithelial differentiation. Large intestine has no Paneth cells and villi; therefore, it has a relatively flat surface. The upward migration of cells from crypts ends with their incorporation into surface epithelium cuff, and each cuff is supplied by one crypt, unlike in the small intestine, where each villous receives cellular outputs from several surrounding crypts [6,38]. Differentiated cells in the colon are also derived from CBC, and their turnover time in colonic mucosa is ∼3 to 4 days.

Copyright © 2011 by Morgan & Claypool Life Sciences.
Bookshelf ID: NBK54099
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