L iver fibrosis is characterized by an increase in the synthesis and deposition of extracellular matrix proteins, including type I collagen. The activated hepatic stellate cell (HSC) is responsible for increased type I collagen synthesis during liver fibrosis. After a fibrogenic stimulus, the HSC undergoes a complex phenotypic change from a quiescent vitamin A-storing cell to that of an activated, myofibroblast-like cell (reviewed in Friedman 1 and Eng et al. 2 ). Numerous changes occur during HSC activation, including the loss of retinoid stores, the appearance of smooth muscle ␣-actin, and a dramatic increase in the synthesis of type I collagen.Type I collagen is the product of 2 genes, the ␣1(I) and the ␣2(I) genes. Although located on different chromosomes, these genes are coordinately regulated in a developmental, tissue-specific, and inducible manner. [3][4][5][6] Previous studies have shown that ␣1(I) collagen gene expression is increased during HSC activation at both the transcriptional and posttranscriptional levels. 7-9 Transcriptional regulatory elements have been identified in the 5Ј-flanking region, the promoter region, first intron, and 3Ј-flanking region of both type I collagen genes in several species. [10][11][12][13][14][15][16][17][18][19][20][21][22][23] Several deoxyribonuclease (DNase) I-hypersensitive sites (HSs) have been identified in the 5Ј-flanking region of the murine ␣1(I) collagen gene that are present in collagen-producing, but not in non-collagenproducing cells, suggesting that these elements are in-

A modified procedure for analysis of RNA in denaturing formamide-polyacrylamide slab gels containing 6 M urea is described. Using this technique, in conjucntion with fluorographic analysis, we determined molecular weights and molar ratios of the various vesicular stomatitis virus (VSV) induced RNAs in BHK21 cells. A comparison of the molar ratios of virus-specific mRHAs and their putative protein products in these cells suggests that there is little, if any, translational control of viral gene expression during acute VSV infection.

We have identified two blocks of regulatory sequences located in the 5'-flanking region and the first intron of the mouse alpha 1 type I collagen (COLlAl) gene. Both blocks were found to contain positive as well as negative regulatory elements. Sequences located within 222 base pairs upstream of the transcription start site showed a strong stimulatory effect on the COLlAl promoter and were sufficient for tissue-specific regulation of the COLlAl gene. The combined upstream and intron regulatory sequences showed a marked inhibition of

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