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Glutamine Synthetase Serves as an Accurate Immunohistological Marker for Perivenular Hepatocytes in the Liver
Author(s) -
Mak Ki M.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.511.2
Subject(s) - axin2 , hepatocyte , lobules of liver , immunohistochemistry , pathology , biology , glutamine synthetase , microbiology and biotechnology , chemistry , glutamine , medicine , wnt signaling pathway , biochemistry , amino acid , in vitro , signal transduction
In the mouse liver, Axin2 (axis inhibition protein 2) is selectively expressed in hepatocytes that form a single layer surrounding the central vein, defined as perivenular hepatocytes. Axin2 hepatocytes display hepatocyte stem cell‐like properties. These cells self‐renew and their progenies migrate from the centrilobular zone towards the periportal area, replacing lobular uninjured or senescent hepatoytes and contributing to physiological turnover of parenchymal cells. In one year, Axin2 cells replenish on average 40% of hepatocytes in the liver under normal conditions. Axin2 cells also express glutamine synthetase (GS), which detoxifies the ammonia entering the liver circulation. However, both Axin2 and GS expression is maintained by the Wnt/β‐catenin pathway derived from the central vein endothelium. Because no suitable antibody that detects perivenular Axin2 expression by immunohistochemistry is available to date, GS has been used as a surrogate marker for Axin2 to stain perivenular hepatocytes. The present study tested whether GS serves as a marker for perivenular hepatocytes and evaluated the effects of fibrogenesis on the lobular distribution of GS‐positive cells in the human liver using cadaveric liver samples. Immunoperoxidase staining with a polyclonal GS antibody revealed that in the liver with minimal fibrosis (N = 8), GS selectively stained perivenular hepatocytes generally arranged in 1–3 layers surrounding the central veins. GS‐positive cells were also seen as a single layer along the larger collecting veins. There was a variable presence of small aggregates of GS‐positive non‐perivenular hepatocytes in the centrilobular zone. The GS immunoreactivity in hepatocytes was cytoplasmic. No GS staining of periportal hepatocytes was seen. A similar distribution of GS‐positive hepatocytes was observed in the liver showing advanced stages of septal fibrosis (N = 8), bridging fibrosis (N = 8) and incomplete cirrhosis (N = 6). In end‐stage cirrhosis (N = 4), GS expression could not be observed around the central veins in the nodular parenchyma. Conclusions GS serves as an accurate immunohistological marker for perivenular hepatocytes that are considered as hepatocyte stem cells in the mouse. GS expression in non‐perivenular hepatocytes in the centrilobular zone suggests an expansion of perivenular hepatocytes in response to hepatic fibrogenesis. Loss of perivenular GS expression in cirrhosis may reflect a disruption of contact between the central vein endothelium and perivenular hepatocytes. Understanding the histogenesis of GS expressing perivenular hepatocytes may help in therapeutic planning for enhancing hepatic regeneration in liver fibrosis disease. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .