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, Nort hern-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 ribo nucleic acid expression was low in normal liver, and comfined to mesen chymal cells of portal tract stroma, vessel walls and perisinusoidal s pace. In fibrotic liver, undulin deposition and gene expression were e nhanced in fibrotic stroma and areas of fibrogenesis identified by the presence of active septa and inflammatory ifiltrate. Undulin gene exp ression in fibrotic liver was exclusively localized in mesenchymal cel ls that could be identified by staining for vimentin, and partially fo r alpha-smooth muscle actin as (myo)fibroblasts, and possibly fat stor ing cells. These data suggest that undulin is a constituent of the hep atic extracellular matrix of normal human liver, and that it participa tes in the rearrangement of connective tissue occurring in hepatic fib rosis.