In situ hybridization for procollagen types I, III and IV mRNA in normal and fibrotic rat liver: evidence for predominant expression in nonparenchymal liver cells.

The expression of alpha 2(I), alpha 1(III) and alpha 1(IV) procollagen mRNA was analyzed in normal and CCl4-induced fibrotic rat liver by in situ hybridization using RNA probes. In normal liver, moderate amounts of alpha 2(I) and alpha 1(III) procollagen transcripts were found in sinusoidal cells, in stromal cells of the portal tracts and in the vicinity of central veins, whereas a1(IV) procollagen gene expression was below the threshold of detection. After 2 weeks of CCl4 treatment, increased transcription of alpha 2(I) and alpha 1(III) procollagen genes was observed in sinusoidal cells. At this stage, alpha 1(IV) procollagen mRNA was detectable in the same cell types and localization as alpha 2(I) and alpha 1(III) procollagen transcripts, although with a weaker signal. After 4 weeks, newly formed fibrous septa showed many cells intensely labeled by alpha 2(I), alpha 1(III) and alpha 1(IV) procollagen probes. Neither in normal liver nor at any stage of fibrosis was any hybridization signal above background observed in hepatocytes. These patterns suggest that in the liver Type I, Type III and Type IV procollagen expression takes place predominantly in nonparenchymal cells. Therefore, hepatocytes do not appear to be significantly involved in procollagen production in this experimental model of liver fibrosis.