Delay in hepatocyte proliferation and prostaglandin D2 synthase expression for cholestasis due to endotoxin during partial hepatectomy in rats

• Published in: Molecular medicine reports Vol. 20; no. 5; pp. 4367 - 4375
• Main Authors: Wakasa, Yusuke, Kimura, Norihisa, Yamada, Toshiyuki, Shimizu, Takeshi, Hakamada, Kenichi, Tsuchida, Shigeki
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications 01.11.2019; Spandidos Publications UK Ltd; D.A. Spandidos
• Subjects: Acids; Animals; Antigens; Bile; Bile acids; Bile Acids and Salts - blood; Bile Acids and Salts - metabolism; Bilirubin - blood; Biochemistry; Biomarkers; CD163 antigen; Cell adhesion & migration; Cell Proliferation; Chemokine CXCL9 - genetics; Chemokine CXCL9 - metabolism; Chemokines; Cholestasis; Cholestasis - etiology; Cholestasis - metabolism; Deoxycholic acid; Disease Models, Animal; DNA microarrays; EDTA; Endotoxins - adverse effects; Gallbladder diseases; Gene expression; Gene Expression Regulation; Growth factors; Health aspects; Hepatectomy; Hepatocytes; Hepatocytes - metabolism; Immunohistochemistry; Infection; International economic relations; Intramolecular Oxidoreductases - genetics; Intramolecular Oxidoreductases - metabolism; Kupffer cells; Kupffer Cells - metabolism; Laboratory animals; Ligands; Lipocalins - genetics; Lipocalins - metabolism; Lipopolysaccharides; Liver; Liver transplantation; Localization; Macrophages; Male; Mitogens; Organ transplantation; Polymerase chain reaction; Polypeptides; Proliferating cell nuclear antigen; Prostaglandin D2; Prostaglandin D2 synthase; Prostaglandins; Rats; Reductase; Reverse transcription; RNA, Messenger - genetics; Rodents; Scientific equipment industry; Sodium; Surgery; Transcription (Genetics); Western blotting; United States
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2019.10681

Infection is a frequent complication of liver transplantation or partial hepatectomy (PH) and sometimes results in cholestasis. We examined factors involved in infection‑induced cholestasis after PH, employing a rat PH model and lipopolysaccharide (LPS) as a bacterial toxin. Male Sprague‑Dawley rats were subjected to 70% PH and/or LPS injection, and tissues were harvested at 0, 24, 72 and 168 h. Gene expression was analyzed by microarray analysis and reverse transcription‑quantitative polymerase chain reaction, and protein levels and localization were analyzed by western blotting and immunohistochemistry, respectively. Plasma bile acid levels were significantly higher in the LPS + PH group than in the PH group. Ribonucleotide reductase regulatory subunit M2 and proliferating cell nuclear antigen peaked at 24 and 72 h in the PH group and LPS + PH group, respectively, indicating a delay in cell proliferation in the latter group. The sodium‑dependent taurocholate cotransporting polypeptide and organic‑anion‑transporting polypeptide 1a1 and 1a2 were reduced in the PH group at 24 h, and were not further decreased in the LPS + PH group. Chemokine ligand 9 (Cxcl9), a chemokine involved in M2 macrophage polarization, increased after 24 h in the LPS and the LPS + PH groups. The number and shape of Cxcl9‑positive cells were similar to CD163‑positive cells, suggesting that such cells produced the chemokine. Hematopoietic prostaglandin D2 synthase (Ptgds2) was only detected in hepatocytes of the LPS + PH group exhibiting a delay in cell proliferation. Thus, Kupffer cells activated with LPS were suggested to be responsible for a delay in hepatocyte proliferation after PH.