Exogenous nucleosides modulate the expression of rat liver extracellular matrix genes in single cultures of primary hepatocytes and a liver stellate cell line and in their co-culture.
OBJECTIVE
We have previously reported the antifibrotic effect of dietary nucleotides in cirrhotic rats. In this work, we used primary rat hepatocytes, a liver stellate cell line (CFSC-2G) and co-cultures of both cell types to investigate the effects of exogenous nucleosides on the gene expression of various extracellular matrix components and on markers of liver function, and to ascertain whether the effects found in vivo are due to CFSC-2G, hepatocytes, or are the consequence of cell-cell interactions.


RESULTS
Nucleosides enhanced fibronectin, laminin, and alpha1(I) procollagen levels in CFSC-2G and hepatocytes, as well as collagen synthesis and secretion in CFSC-2G. In contrast, nucleosides lowered fibronectin, laminin and alpha1(I) procollagen levels, and decreased collagen synthesis in co-cultures. Matrix metalloproteinase-13 content and collagen secretion increased in co-cultures incubated with nucleosides. Albumin increased in hepatocytes and co-cultures incubated in the presence of nucleosides.


CONCLUSIONS
Nucleosides modulate the production of extracellular matrix in single cultures of hepatocytes and of CFSC-2G, and in co-cultures. This effect seems to be regulated at the translational level. The opposite behavior of single cultures and co-cultures is probably due to the fact that the latter model reproduces many of the physical and functional relationships observed in vivo between hepatocytes and stellate cells.
Arnaud
A
A
R&D Department, Abbott Laboratories, Granada, USA.
Fontana
L
L
Sáez-Lara
M J
MJ
Gil
A
A
López-Pedrosa
J M
JM
D000818:Animals; D002460:Cell Line; D018920:Coculture Techniques; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D007797:Laminin / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000502:physiology; D008297:Male; D023421:Models, Animal; D009705:Nucleosides / Q000008:administration & dosage*; D011347:Procollagen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D007797:Laminin; D009705:Nucleosides; D011347:Procollagen; D003094:Collagen