title: Intestinal involvement during 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced chronic liver injury in a mouse model.
abstract: OBJECTIVE
  Although a physiologic relationship between intestinal mucosal integrity and hepatic function has been previously described, the effect of primary liver disease on intestinal mucosal homeostasis has not been previously well documented. In the current study, we studied the effects of chronic liver injury as a primary injury on enterocyte turnover (proliferation and apoptosis) in a mouse model.
  
  
  METHODS
  The liver toxin 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-enriched diet was used to induce chronic cholestatic liver injury in mice. Livers and intestine were harvested after 3 weeks of dietary treatment of histologic analysis and a determination of cell proliferation (immunohistochemistry for Ki67), or apoptosis (immunohistochemistry for caspase-3), as well as a determination of Wnt/β-catenin signaling activity.
  
  
  RESULTS
  All DDC-fed animals exhibited histologic evidence of liver damage that was associated with the expansion of atypical ductal proliferation near the periportal areas and increased oxidative stress. In the intestine, DDC-induced liver damage was associated with decreased villus height, decreased enterocyte proliferation, and increased cell apoptosis compared with control animals. There was also evidence for decreased β-catenin expression by immunostaining in crypt and villus cells of DDC-fed mice compared with control animals.
  
  
  CONCLUSIONS
  Primary liver injury and cholestasis is associated with intestinal mucosal hypoplasia. Decreased cell proliferation and increased cell apoptosis may be responsible for decreased intestinal epithelial cell mass. The observed decrease in cell turnover is accompanied by an alteration in Wnt/β-catenin signaling.
authors.affiliation: Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. igor-dr@internet-zahav.net
authors.forename: Igor
authors.initials: I
authors.lastname: Sukhotnik
authors.forename: Unsal
authors.initials: U
authors.lastname: Kuscuoglu
authors.forename: Banu
authors.initials: B
authors.lastname: Altindag
authors.forename: Guo-Zhong
authors.initials: GZ
authors.lastname: Tao
authors.forename: Nadja
authors.initials: N
authors.lastname: Lehwald
authors.forename: Karl G
authors.initials: KG
authors.lastname: Sylvester
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D056487:Chemical and Drug Induced Liver Injury, Chronic / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D003997:Dicarbethoxydihydrocollidine; D004195:Disease Models, Animal; D020895:Enterocytes / Q000502:physiology; D007410:Intestinal Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051153:Wnt Proteins; D051176:beta Catenin; D003997:Dicarbethoxydihydrocollidine