Alternative splicing products of the tenascin gene distinguish rat liver fat storing cells from arterial smooth muscle cells and skin fibroblasts

Abstract

Fat storing-(Ito-)cells (FSC) transform into a myofibroblast-like cell type during liver fibrogenesis. A similar development can be observed in cell culture. At the moment, a definite marker to differentiate transformed FSC from smooth muscle cells (SMC) is not available. We recently found that FSC, SMC and skin fibroblasts (SF) synthesize tenascin, a novel matrix protein. As it is reported that various tissues express different tenascin forms by the mechanism of alternative pre-mRNA splicing, we analyzed the tenascin transcripts in these cell types. Total RNA extracted from cultured FSC, SMC and SF, analyzed by Northern blot hybridization, showed a 7.2 kb transcript in FSC, a 8.7 kb mRNA in SMC, whereas SF produced both messages. As the splicing pattern of FSC in primary culture did not change after passaging, this differential expression of tenascin mRNA might provide a tool to identify myofibroblast-like cells derived from FSC. The important fibrogenic mediator transforming growth factor-β (TGF-β) increased tenascin gene expression in each cell type. In SMC, TGF-β additionally induced the production of the 7.2 kb transcript. Determination of tenascin transcripts will allow to examine the purity of FSC cultures and facilitate a better identification of the cells involved in liver fibrosis.