Sequential changes in intercellular junctions between hepatocytes during the course of acute liver injury and restoration after thioacetamide treatment.
Sequential changes of gap junctions (GJs), tight junctions (TJs) and desmosomes (DSs) between hepatocytes during restorative proliferation were studied in rats after a single intraperitoneal administration of 200 mg/kg thioacetamide (TAA). Antibody against connexin 32 was used to demonstrate GJs; simultaneously the changes in TJs and DSs were studied using antibodies against 7H6 protein and desmoplakins. Propidium iodide and bromodeoxyuridine were used to recognize necrotic and proliferative cells. GJs were evenly distributed in early necrotic hepatocytes at 16 h after TAA treatment, then disappeared from necrotic and surrounding cells at 24 h. At 48 h, GJs had disappeared completely from hepatocytes in whole liver lobules, while many hepatocytes were heavily labelled with BrdU. At 72 h, GJs reappeared, firstly in perinecrotic areas. At 96 h after treatment, when the injured areas had disappeared and restorative proliferation ceased, GJs were distributed evenly throughout the lobules. Immunohistochemical observation of GJs in centrilobular, perinecrotic and periportal areas after TAA-induced hepatic necrosis was confirmed by counting the number of connexin-32-positive spots in the respective areas. TJs and DSs disappeared from necrotic cells at 24 h, but then increased between 24 and 48 h in perinecrotic areas, though the increased intensity of these junctions was more evident at 48 h. At 72 h, localization of TJs and DSs returned to normal. These results suggest that during the course of acute hepatic injury, GJs (cell-cell communication) behave differently from other intercellular junctions.
Kojima
T
T
Department of Pathology, Sapporo Medical University School of Medicine, Japan.
Sawada
N
N
Zhong
Y
Y
Oyamada
M
M
Mori
M
M
D000818:Animals; D001973:Bromodeoxyuridine; D002455:Cell Division; D003896:Desmosomes / Q000187:drug effects / Q000648:ultrastructure; D017629:Gap Junctions / Q000187:drug effects / Q000648:ultrastructure; D007150:Immunohistochemistry; D007365:Intercellular Junctions / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure*; D007700:Kinetics; D008099:Liver / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D009336:Necrosis; D011419:Propidium; D051381:Rats; D011916:Rats, Inbred F344; D013853:Thioacetamide / Q000633:toxicity*; D013997:Time Factors
D013853:Thioacetamide; D011419:Propidium; D001973:Bromodeoxyuridine