Discussion: Growth Factor Regulation

The epithelial populations found throughout the gastrointestinal tract exhibit a relatively high rate of turnover throughout postnatal life. The maintenance of normal cellularity in the setting of continuous proliferation, differentiation, and cell senescence implies the presence of exquisite regulation of cell turnover. In addition, regulatory mechanisms must provide plasticity in order to facilitate reconstitution of mucosal integrity following injury. While undoubtedly cell proliferation and mucosal growth are modulated by a wide variety of influences, including extracellular matrix constituents and nutrient availability, it is clear that a number of peptides with growth modulatory properties play an important role in the gastrointestinal tract. Although the full diversity of the peptide growth factors which regulate mucosal growth in the gastrointestinal tract remains to be determined, several important peptide growth factors discussed in this section have been demonstrated to contribute to growth and proliferation in gastrointestinal tract mucosa. From the study of these factors, some general themes of peptide growth factor action in the gastrointestinal tract have emerged. First, growth in the mature gastrointestinal tract is modulated by structurally diverse proteins. Second, these proteins act through a variety of mechanisms. Third, these proteins often exhibit distinct functional properties in addition to their capability to stimulate or inhibit growth [1]. Fourth, these proteins may play essential roles in response to mucosal injury in addition to their role in constitutive regulation of normal mucosal turnover. A corollary of the latter is that alterations in growth factor expression may contribute to the pathogenesis of mucosal disease. A brief overview of observations supporting each of these themes is reinforced by the papers in this section. It should be noted, however, that the delineation of a coherent view of the interrelationships between the various proteins that comprise a network of peptide growth factors will be necessary in order to achieve an accurate estimation of the role of each factor in normal mucosal homeostasis and in pathologic states.