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 host 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, including nutrients or other dietary factors, secretions, and microbes that occur within the lumen and distribute over a proximal-to-distal gradient, are also crucial for maintenance of normal gut mucosal regeneration and could explain the villous-height-crypt-depth gradient and variety of adaptation, since these factors are diluted, absorbed, and destroyed as they pass down the digestive tract. Recently, intestinal stem cells, cellular polyamines, and noncoding RNAs are shown to play an important role in the regulation of gastrointestinal mucosal growth under physiological and various pathological conditions. In this book, we highlight key issues and factors that control gastrointestinal mucosal growth and homeostasis, with special emphasis on the mechanisms through which epithelial renewal and apoptosis are regulated at the cellular and molecular levels.
Table of Contents
Intestinal Architecture and Development
Characteristics of Gut Mucosal Growth
Intestinal Stem Cells
Role of GI Hormones on the Gut Mucosal Growth
Peptide Growth Factors in GI Mucosal Growth
Luminal Nutrients and Microbes in Gut Mucosal Growth
Polyamines in the Regulation of Mucosal Growth
Noncoding RNAs in Gut Mucosal Growth and Epithelium Integrity
Summary and Conclusions
About the Author(s)Rao N. Jaladanki
, University of Maryland School of Medicine
Rao N. Jaladanki received his PhD degree in endocrinology from Sri Venkateswara University, Tirupati, AP, India in 1992. His research has been highly focused on gut physiology, particularly in the regulation of mucosal growth and repair under biological and various pathological conditions over the past 20 years. The goal of Dr. Rao's research is to specifically define the roles and mechanisms of cellular polyamines in gut epithelial cell proliferation, growth arrest, apoptosis, and migration. Dr. Rao is an Associate Professor at the University of Maryland School of Medicine, and he has published more than 100 peer-reviewed papers, 7 book chapters, and several review articles. He has also held a position as Research Health Scientist at Biomedical Research Service, US Department of Veterans Affairs, over the past 6 years.Jian-Ying Wang
, University of Maryland School of Medicine
Dr. Jian-Ying Wang is the Joseph and Corinne Schwartz endowed professor of surgery and professor of pathology at the University of Maryland School of Medicine at Baltimore (UMB). He is also an associate chair for Basic Research, Department of Surgery at UMB and a senior research career scientist, Biomedical Research Service, US Department of Veterans Affairs. Dr. Wang is a world-renowned gastrointestinal physiologist and a leading investigator in the field of basic surgical sciences. His research focuses on the gut mucosal homeostasis/barrier function, particularly the roles of cellular polyamines, RNA-binding proteins, and noncoding RNAs. Dr. Wang has authored many seminal research accomplishments throughout his career. He first reported that polyamines stimulate repair of damaged mucosa and are crucial for maintaining the gut epithelial integrity. His group further found that polyamines up-regulate expression of growth-promoting genes by increasing gene transcription but down-regulate growth-inhibiting genes through destabilization of mRNAs. His group has elucidated critical mechanism underlying posttranscriptional regulation by polyamines, finding that polyamines regulate the stability and translation of mRNAs via RNA-binding proteins and microRNAs. Importantly, Dr. Wang's research projects are directly relevant to patients with mucosal injury-associated diseases, barrier dysfunction, inflammation, and sepsis. Dr. Wang's current work is highly focused on the regulation of gut epithelial regeneration and permeability by RNA-binding proteins and noncoding RNAs such as microRNAs and long noncoding RNAs. The aim of these ongoing studies is to define the link between the posttranscriptional gene regulation and mucosal injury/repair, inflammation, leaky gut, and sepsis. Dr. Wang's research program has added depth and a higher level of sophistication to our biomedical research community in general. Dr. Wang's research program has been continuously funded by multiple NIH grants and VA Merit-Review grants for more than 20 years. His service to the scientific community is also exceptional, as Dr. Wang serves as a member of multiple NIH study sections and VA-MERIT Review study sections, and is also on the editorial board for several scientific journals. Dr. Wang has successfully mentored young scientists and junior faculty. During the past 5 years, more than 20 junior faculty members, surgical residents, research fellows, and graduate students have worked at Dr. Wang's group, and six trainees under Dr. Wang's mentorship received NIH grants, VA Career Development Awards, and VA MERIT-Review Awards.