Expression of a 72-kDa heat shock protein, and its cytoprotective function, in gastric mucosa in cirrhotic rats

J Gastroenterol. 2004 Aug;39(8):724-33. doi: 10.1007/s00535-003-1380-8.

Abstract

Background: Portal hypertensive gastropathy (PHG) is a clinical entity that is observed frequently in patients with liver cirrhosis. In PHG, gastric mucosa is highly susceptible to mucosal injury caused by noxious agents. Many studies, including ours, have reported that a 72-kDa heat shock protein (HSP72) has a crucial cytoprotective function in gastric mucosa. In this study, we investigated the expression and cytoprotective effect of HSP72 on gastric mucosa in portal hypertensive rats.

Methods: PHG was produced by bile duct ligation (BDL) or carbon tetrachloride administration in male Sprague-Dawley rats. The expression of HSP72 in the gastric mucosa was evaluated by Western blotting. Induction of gastric mucosal HSP72 by 6-h water-immersion stress was compared between cirrhotic and control rats. Also, mucosal protective abilities against hydrochloric acid (HCl; 0.6 N) following pretreatment with water-immersion stress to induce HSP72 were studied in both groups.

Results: Portal venous pressure was significantly higher in cirrhotic rats compared with control rats ( P < 0.05). Baseline expression (before water-immersion stress) of mucosal HSP72 was significantly lower in cirrhotic rats compared with control rats. HCl-induced gastric mucosal lesions were significantly suppressed in control rats compared with cirrhotic rats, especially when HSP72 was preinduced by water-immersion stress.

Conclusions: These findings suggest that HSP72 in the gastric mucosa plays a crucial role with respect to cytoprotection; the induction of HSP72 may provide therapeutic strategies for protection against mucosal injury in PHG.

MeSH terms

  • Animals
  • Cell Count
  • Cell Survival / physiology*
  • Gastric Acidity Determination
  • Gastric Mucosa / pathology*
  • HSP72 Heat-Shock Proteins
  • Heat-Shock Proteins / physiology*
  • Hypertension, Portal / pathology*
  • Liver Cirrhosis, Experimental / pathology*
  • Male
  • Parietal Cells, Gastric / pathology
  • Proton Pumps / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Stomach Ulcer / pathology
  • Stress, Psychological / complications

Substances

  • HSP72 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Proton Pumps