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- Title
Delay in hepatocyte proliferation and prostaglandin D2 synthase expression for cholestasis due to endotoxin during partial hepatectomy in rats.
- Authors
Wakasa, Yusuke; Kimura, Norihisa; Yamada, Toshiyuki; Shimizu, Takeshi; Hakamada, Kenichi; Tsuchida, Shigeki
- Abstract
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.
- Subjects
CYCLOOXYGENASES; ENDOTOXINS; PROLIFERATING cell nuclear antigen; RIBONUCLEOSIDE diphosphate reductase; KUPFFER cells; HEPATECTOMY
- Publication
Molecular Medicine Reports, 2019, Vol 20, Issue 5, p4367
- ISSN
1791-2997
- Publication type
Article
- DOI
10.3892/mmr.2019.10681