Liver fat-storing cell clones obtained from a CCl4-cirrhotic rat are heterogeneous with regard to proliferation, expression of extracellular matrix components, interleukin-6, and connexin 43.
BACKGROUND
Immunocytochemical analysis of liver has revealed that fat-storing cells (FSC) are heterogeneous with regard to vitamin A content, staining for cytokeratins, desmin, and vimentin and the cytoskeletal protein alpha-smooth muscle actin. Since fat-storing cells play an important role in collagen deposition in normal and cirrhotic liver, we considered it important to study whether fat-storing cells were heterogeneous with regard to cell proliferation, expression of mRNAs coding for cytokines interleukin-6 (IL-6) and transforming growth factor-beta (TGF-beta), and extracellular matrix components alpha 1(I), alpha 1(III), alpha 1(IV) procollagens, laminin B1 chain and fibronectin.


METHODS
We used a FSC line (CFSC) that was developed in our laboratory after spontaneous immortalization of a primary culture of fat-storing cells that were obtained from the liver of a CCl4-cirrhotic rat (Lab. Invest. 65:644-653, 1991). The cells were cloned by limiting dilution and have been maintained in culture for over 3 years without appreciable changes in the parameters investigated.


RESULTS
In this communication we report the characterization of 4 of the clones obtained. We show that they are heterogeneous with regard to proliferation index, expression of alpha 1(I), alpha 1(III) and alpha 1(IV) procollagen, IL-6 and TGF-beta mRNAs. The clones also differ in their response to IL-6. We also showed that clones are coupled through functional gap junctions but that they are heterogeneous with regard to the expression of the gap junction protein connexin 43.


CONCLUSIONS
We suggest that clonal heterogeneity of FSC may occur in vivo. Since each of the clones expresses a unique phenotype, these FSC clones could be excellent models to study the role of defined extracellular matrices on the expression of liver specific genes by cultured hepatocytes.
Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York.
P
P
Greenwel
J
J
Rubin
M
M
Schwartz
E L
EL
Hertzberg
M
M
Rojkind
D000818:Animals; D002251:Carbon Tetrachloride; D002455:Cell Division; D002999:Clone Cells; D017630:Connexins; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D016212:Transforming Growth Factor beta / Q000235:genetics
D017630:Connexins; D016326:Extracellular Matrix Proteins; D015850:Interleukin-6; D008565:Membrane Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D002251:Carbon Tetrachloride