Zonation of Nitrogen and Glucose Metabolism Gene Expression upon Acute Liver Damage in Mouse

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.

Potassium diformate influences gene expression of GH/IGF-I axis and glucose homeostasis in weaning piglets

“…It is reported that, hepatic IGF-I acted directly on the hepatocytes in a GH-independent manner, regulated hepatocytes cell proliferation, differentiation and metabolism (Takahashi., 2012;Pivonello et al, 2014). Present observation agree with this, KDF treatment did not change the level of HDL, LDL, TC, TG and BG, but it dramatically increased the mRNA expressions of PCK, G6PC, and FBPase in liver, which are the key regulatory enzymes for hepatic gluconeogenesis (Ghafoory et al, 2013). In liver, PCK catalyzes the first committed step in gluconeogenesis.…”

Tissue Repair in the Mouse Liver Following Acute Carbon Tetrachloride Depends on Injury‐Induced Wnt/β‐Catenin Signaling

“…). The local effect of CCl 4 is due to the zonated expression of CYP2E1, the major P450 cytochrome that metabolizes CCl 4 . In order to determine whether Wnt signaling is activated following acute CCl 4 injury, we conducted in situ hybridization for the Wnt target gene, Axin2 .…”

Tissue repair in the mouse liver following acute carbon tetrachloride depends on injury-induced Wnt/β-catenin signaling

“…CCl4 injury leads to centrilobular necrosis within 48 hours of CCl4 administration (Supplemental Figure 1). The local effect of CCl4 is due to the zonated expression of CYP2E1, the major P450 cytochrome that metabolizes CCl4 (28). In order to determine whether Wnt signaling is activated following acute CCl4 injury, we conducted in situ hybridization for the Wnt target gene, Axin2 (19,29).…”