Reciprocal changes in trefoil 1 and 2 expression in stomachs of mice with gastric unit hypertrophy and inflammation

J Pathol. 2005 Sep;207(1):43-52. doi: 10.1002/path.1811.

Abstract

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.

MeSH terms

  • Animals
  • Autoimmune Diseases / metabolism
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Cytokines / physiology
  • Disease Models, Animal
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / pathology*
  • Gastrins / blood
  • Gastritis / metabolism*
  • Gene Expression Regulation
  • H(+)-K(+)-Exchanging ATPase / deficiency
  • H(+)-K(+)-Exchanging ATPase / genetics
  • Hyperplasia / metabolism
  • Hypertrophy / metabolism
  • Interleukin-11 / biosynthesis
  • Interleukin-11 / genetics
  • Interleukin-11 / physiology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Mutant Strains
  • Mucins / genetics
  • Mucins / metabolism*
  • Mucins / physiology
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Muscle Proteins / physiology
  • Peptides / genetics
  • Peptides / metabolism*
  • Peptides / physiology
  • RNA, Messenger / genetics
  • Species Specificity
  • Trefoil Factor-1
  • Trefoil Factor-2

Substances

  • Cytokines
  • Gastrins
  • Interleukin-11
  • Mucins
  • Muscle Proteins
  • Peptides
  • RNA, Messenger
  • TFF2 protein, mouse
  • Tff1 protein, mouse
  • Trefoil Factor-1
  • Trefoil Factor-2
  • H(+)-K(+)-Exchanging ATPase