It0 cells are perisinusoidal cells thought to be a major source of collagen in normal and fibrotic livers. These cells appear to have features similar to several cell types but when cultured assume a fibroblast-like morphology.
In this study we evaluated the phenotype of both freshly isolated and cultured Ito cells by examining their gene expression. To better define the modulators of Ito-cell collagen synthesis, we also examined the effect of trans- forming growth factor-pl, tumor necrosis factor-ar and dexamethasone on collagen synthesis by these cells. Northern hybridization analysis revealed that cul- tured It0 cells expressed different types of procollagen mRNAs than did freshly isolated cells. Cultured cells contained large amounts of type I procollagen mRNA and lesser amounts of types I11 and IV, whereas freshly isolated cells contained more type IV procollagen mRNA than types I and 111. Treatment of cultured cells with either transforming growth factor-pl or tumor necrosis factor-ol resulted in a greater than threefold increase in total collagen content, and the effects of these cytokines on Ito-cell collagen synthesis in- volved different levels of gene regulation. Transforming growth factor-pl-treated cells had an approximately threefold increase in their type I procollagen mRNA levels, whereas no increase in this mRNA level was found in tumor necrosis factor-a-treated cells. Transforming growth factor-pl treatment induced a twofold increase in transforming growth factor-pl mRNA content in cultured cells. In contrast to transforming growth factor-pl, dexamethasone inhibited type I procollagen and transforming growth factor-pl mRNA content by at least twofold in cultured cells. These results suggest that cultured Ito cells alter their collagen gene expression such that they become phenotypically more fibroblast-like. Furthermore, transforming growth factor-pl's induction of its own mRNA in Ito cells suggests that these cells are capable of amplifying