Liver fat-storing cell clones obtained from a CC1₄-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 α-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-β (TGF-β), and extracellular matrix components α1(I), α1(III), α1(IV) procollagens, laminin B1 chain and fibronectin. EXPERIMENTAL DESIGN: 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 α1(I), α1(III) and α1(IV) procollagen, IL-6 and TGF-β 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.