Up-regulation of uPARAP/Endo180 during culture activation of rat hepatic stellate cells and its presence in hepatic stellate cell lines from different species.
BACKGROUND
The urokinase plasminogen activator receptor associated protein (uPARAP)/Endo180 is a novel endocytic receptor that mediates collagen uptake and is implicated to play a role in physiological and pathological tissue-remodelling processes by mediating intracellular collagen degradation.


RESULTS
This study investigates the expression of uPARAP/Endo180 protein and messenger RNA in primary rat hepatic stellate cell (HSC) cultures. The results show that uPARAP/Endo180 protein is not expressed in freshly isolated HSCs or during the first few days of culture while the cells still display quiescent features. In contrast, uPARAP/Endo180 protein is expressed early during HSC activation when cells are transdifferentiated into myofibroblast-like cells. Very low levels of uPARAP/Endo180 mRNA are detectable during the first days of culture but uPARAP/Endo180 mRNA is strongly up-regulated with increasing time in culture. Moreover, endocytic uptake of denatured collagen increases as transdifferentiation proceeds over time and correlates with increased expression of uPARAP/Endo180. Finally, analysis of uPARAP/Endo180 expression in four hepatic stellate cell lines from three different species showed that all these cell lines express uPARAP/Endo180 and are able to take up denatured collagen efficiently.


CONCLUSIONS
These results demonstrate that uPARAP/Endo180 expression by rat HSCs is strongly up-regulated during culture activation and identify this receptor as a feature common to culture-activated HSCs.
Department of Molecular Biosciences, University of Oslo, Blindernveien 31, Blindern, Oslo, Norway. s.a.mousavi@imbv.uio.no
Seyed A
SA
Mousavi
Marita S
MS
Fønhus
Trond
T
Berg
D000818:Animals; D002460:Cell Line; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000378:metabolism*; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011975:Receptors, Mitogen / Q000235:genetics / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
C408294:Endo180; D012333:RNA, Messenger; D011975:Receptors, Mitogen; D055293:Receptors, Urokinase Plasminogen Activator; D003094:Collagen