Zonation of nitrogen and glucose metabolism gene expression upon acute liver damage in mouse

PLoS One. 2013 Oct 17;8(10):e78262. doi: 10.1371/journal.pone.0078262. eCollection 2013.

Abstract

Zonation of metabolic activities within specific structures and cell types is a phenomenon of liver organization and ensures complementarity of variant liver functions like protein production, glucose homeostasis and detoxification. To analyze damage and regeneration of liver tissue in response to a toxic agent, expression of liver specific enzymes was analyzed by in situ hybridization in mouse over a 6 days time course following carbon tetrachloride (CCl4) injection. CCl4 mixed with mineral oil was administered to BALB/c mice by intraperitoneal injection, and mice were sacrificed at different time points post injection. Changes in the expression of albumin (Alb), arginase (Arg1), glutaminase 2 (Gls2), Glutamine synthetase (Gs), glucose-6-phosphatase (G6pc), glycogen synthase 2 (Gys2), Glycerinaldehyd-3-phosphat-Dehydrogenase (Gapdh), Cytochrom p450 2E1 (Cyp2e1) and glucagon receptor (Gcgr) genes in the liver were studied by in situ hybridization and qPCR. We observed significant changes in gene expression of enzymes involved in nitrogen and glucose metabolism and their local distribution following CCl4 injury. We also found that Cyp2e1, the primary metabolizing enzyme for CCl4, was strongly expressed in the pericentral zone during recovery. Furthermore, cells in the damaged area displayed distinct gene expression profiles during the analyzed time course and showed complete recovery with strong albumin production 6 days after CCl4 injection. Our results indicate that despite severe damage, liver cells in the damaged area do not simply die but instead display locally adjusted gene expression supporting damage response and recovery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon Tetrachloride / toxicity
  • Chemical and Drug Induced Liver Injury / metabolism*
  • Glucose / metabolism*
  • Immunohistochemistry
  • In Situ Hybridization
  • Liver / injuries
  • Liver / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Nitrogen / metabolism*

Substances

  • Carbon Tetrachloride
  • Glucose
  • Nitrogen

Grants and funding

The work was supported by grants of the German Federal Ministry of Education and Research (BMBF) "Virtual Liver" and German Research Foundation (DFG) FOR630 to SD, KBH and SW. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.