Reciprocal changes in trefoil 1 and 2 expression in stomachs of mice with gastric unit hypertrophy and inflammation.
H+/K+-ATPase beta-subunit-deficient mice (129/Sv background) display numerous pathologies in the stomach. Expression of the mutation in BALB/cCrSlc mice results in the development of an aberrant 'mucus-rich' cell population. 'Mucus-rich' cells have been described in stomachs of mice with autoimmune gastritis, a disease mediated by CD4+ T cells. Other pathological features of autoimmune gastritis are similar to those in H+/K+ beta-deficient mice and include a mononuclear cell infiltrate in the gastric mucosa, non-functional or absent parietal cells, depletion of zymogenic cells, hypergastrinaemia, and gastric unit hypertrophy caused by immature cell hyperplasia. The present study investigates further the aberrant gastric 'mucus-rich' cell lineage and analyses the mRNA expression of mucus cell products TFF1 and TFF2. 'Mucus-rich' cells stained for both acidic and neutral mucins, and with a TFF2-specific antibody. Stomachs from both models expressed decreased TFF1 mRNA and reciprocally increased TFF2 mRNA. The involvement of gastrin in regulating trefoil mRNA expression was also investigated using gastrin-deficient mice. In contrast to previous findings, gastrin did not positively regulate TFF1 mRNA expression, but there was possible augmentation of TFF2. Additionally, a clear role for inflammation was established involving both polymorphonuclear and mononuclear cells in these models, and a link was found between mucosal hypertrophy and increased interleukin-11 (IL-11) expression.
Department of Medicine, The University of Melbourne, Western Hospital, Melbourne, VIC 3011, Australia.
T V
TV
Franic
I R
IR
van Driel
P A
PA
Gleeson
A S
AS
Giraud
L M
LM
Judd
D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology*; D005755:Gastrins / Q000097:blood; D005756:Gastritis / Q000378:metabolism*; D005786:Gene Expression Regulation; D017506:H(+)-K(+)-Exchanging ATPase / Q000172:deficiency / Q000235:genetics; D006965:Hyperplasia / Q000378:metabolism; D006984:Hypertrophy / Q000378:metabolism; D017370:Interleukin-11 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009077:Mucins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D010455:Peptides / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D013045:Species Specificity; D000071163:Trefoil Factor-1; D000071164:Trefoil Factor-2
D016207:Cytokines; D005755:Gastrins; D017370:Interleukin-11; D009077:Mucins; D009124:Muscle Proteins; D010455:Peptides; D012333:RNA, Messenger; C481546:TFF2 protein, mouse; C472724:Tff1 protein, mouse; D000071163:Trefoil Factor-1; D000071164:Trefoil Factor-2; D017506:H(+)-K(+)-Exchanging ATPase