Endoreplication and polyploidy in primary culture of rat hepatic stellate cells.
Hepatic stellate cells (HSCs), the pericytes of hepatic sinusoids, and liver myofibroblasts (rMFs), cells located in the portal field and around the pericentral area, are the principal fibrogenic cell types of the liver. In cases of liver damage HSCs undergo "activation," i.e., they acquire a myofibroblast-like appearance and synthesize huge amounts of extracellular matrix proteins (ECMs). Their proliferation ability, however, is a matter of debate. In fact, during culture the number of rat HSCs decreases, while DNA synthesis activity and DNA content per cell increase (4+/-0.6 times). Together with the decrease in cell number (60+/-19% at day 6 of primary culture compared to day 3), cell volume increases and many HSCs become multinuclear. On the other hand, in cultures of rMFs, cell number increases along with DNA synthesis, and these cells do not become multinuclear. "Activated" HSCs produce higher levels of cyclin D(1) and E(1) transcripts than rMFs, which correlates with their increased levels of phosphorylated retinoblastoma (Rb) protein. In activated HSCs DNA synthesis seems to be associated with polyploidy and increase in cell volume, while DNA synthesis is followed by mitosis in rMFs.
Dudas
Jozsef
J
Department of Internal Medicine, Section of Gastroenterology and Endocrinology, Georg-August University Göttingen, Robert-Koch Strasse 40, 37075 Göttingen, Germany.
Saile
Bernhard
B
El-Armouche
Hamudi
H
Aprigliano
Isabella
I
Ramadori
Giuliano
G
D000818:Animals; D017209:Apoptosis; D015152:Blotting, Northern; D002452:Cell Count; D002455:Cell Division; D048429:Cell Size; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000096:biosynthesis; D004247:DNA / Q000032:analysis; D022781:Hepatocytes / Q000166:cytology / Q000502:physiology*; D007150:Immunohistochemistry; D011123:Polyploidy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014316:Tritium
D012333:RNA, Messenger; D014316:Tritium; D019938:Cyclin D1; D004247:DNA; D013936:Thymidine