Growth factors associated with gastric mucosal hypertrophy in autoimmune gastritis.

Abstract	A prominent pathological feature of murine autoimmune gastritis is a pronounced mucosal hypertrophy. Here, we examined factors that may be responsible for inducing this hypertrophy. Because gastrin is known to be both an inducer of gastric mucosal cell proliferation and is elevated in autoimmune gastritis, mice deficient in gastrin were thymectomised at day 3 and assessed for autoimmune gastritis. Gastrin-deficient mice showed all the characteristic features of murine autoimmune gastritis, including gastric unit hypertrophy due to hyperproliferation and accumulation of immature epithelial cells, decreases in the number of zymogenic and parietal cells, and autoantibodies to the gastric H+/K+-ATPase. Hence, gastrin is not required for either the establishment of chronic gastritis or development of the typical pathological features of this disease. We also examined mRNA levels of a number of gastric mucosal growth factors in RNA samples from mice with hypertrophic autoimmune gastritis. Members of the Reg family, RegIIIbeta and RegIIIgamma, were greatly elevated in mice with hypertrophic gastritis, whereas RegI and amphiregulin (an EGF receptor ligand) were more modestly and/or inconsistently induced. These data demonstrate that induction of gastric mitogenic factors, such as members of the Reg family, can be achieved in inflammatory situations by gastrin-independent pathways. Members of the Reg family, in particular RegIIIbeta and RegIIIgamma, are good candidates to be involved in inducing the mucosal hyperproliferation in autoimmune gastritis. These findings are likely to be of relevance to other gastric inflammatory conditions.
Authors	Teo V Franic, Louise M Judd, Nhung V Nguyen, Linda C Samuelson, Kate L Loveland, Andy S Giraud, Paul A Gleeson, Ian R van Driel
Journal	American journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 287 Issue 4 Pg. G910-8 (Oct 2004) ISSN: 0193-1857 [Print] United States
PMID	15205119 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Amphiregulin Areg protein, mouse Autoantibodies EGF Family of Proteins Gastrins Glycoproteins Growth Substances Hbegf protein, mouse Heparin-binding EGF-like Growth Factor Intercellular Signaling Peptides and Proteins Proteins RNA, Messenger RegIII protein, mouse Transforming Growth Factor alpha Epidermal Growth Factor ErbB Receptors H(+)-K(+)-Exchanging ATPase
Topics	Amphiregulin Animals Autoantibodies (immunology) Autoimmune Diseases (pathology, physiopathology) Chronic Disease EGF Family of Proteins Epidermal Growth Factor (genetics) ErbB Receptors (genetics) Gastric Mucosa (immunology, pathology, physiopathology) Gastrins (genetics) Gastritis (immunology, pathology, physiopathology) Gene Expression Glycoproteins (genetics) Growth Substances (genetics) H(+)-K(+)-Exchanging ATPase (immunology) Heparin-binding EGF-like Growth Factor Hypertrophy Intercellular Signaling Peptides and Proteins (genetics) Mice Mice, Inbred BALB C Mice, Mutant Strains Proteins (genetics) RNA, Messenger (analysis) Transforming Growth Factor alpha (genetics)

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