Undulin RNA and protein expression in normal and fibrotic human liver

We have analyzed the distribution, gene expression and cellular origin of undulin, a large extracellular matrix glycoprotein associated with mature collagen fibrils, in human liver by immunohistochemistry, Northern-blot analysis and in situ hybridization. In normal liver, undulin was distributed as densely packed fibers in portal tract stroma, and as fine fibers along sinusoids, and around central veins. Undulin ribonucleic acid expression was low in normal liver, and confined to mesenchymal cells of portal tract stroma, vessel walls and perisinusoidal space. In fibrotic liver, undulin deposition and gene expression were enhanced in fibrotic stroma and areas of fibrogenesis identified by the presence of active septa and inflammatory infiltrate. Undulin gene expression in fibrotic liver was exclusively localized in mesenchymal cells that could be identified by staining for vimentin, and partially for alpha-smooth muscle actin as (myo)fibroblasts, and possibly fat-storing cells. These data suggest that undulin is a constituent of the hepatic extracellular matrix of normal human liver, and that it participates in the rearrangement of connective tissue occurring in hepatic fibrosis.