Extracellular Matrix Proteins of Fibrous Septa in Elderly Cadaveric Livers

The formation of fibrous septa in the liver is a histological hallmark of advanced liver fibrosis that can progress to cirrhosis, the end stage of fibrosis. Liver fibrosis has been shown to be associated with aging and was found to be prevalent in elderly cadavers with a high incidence of septal fibrosis. Using immunoperoxidase staining in paraffin sections, this study assessed the extracellular matrix (ECM) protein constituents of the fibrous septa accompanying septal fibrosis and cirrhosis in the liver of elderly embalmed cadavers. In the developing short septa extending from portal tracts or central veins, the ECM was positively stained for collagens I, III, V, and VI. Elastic fibers—identified by resorcin fuchsin stain—were also present. The staining for these collagens and elastin became more prominent in the bridging septa that link portal tract to portal tract or portal tract to central vein. Some of these septa also contained bile ductules and venules, marked by immunostaining for collagen IV and laminin, two major basement membrane (BM) proteins. Additionally, the venous endothelium expressed factor VIII‐related antigen (FVIIIRAg). In cirrhosis, the fibrotic bands showed conspicuous staining for all these collagens and proteins Conclusion There are at least eight proteins present in the septa: fibrillar collagens I, III, and V, microfilamentous collagen VI, elastin, BM collagen IV and laminin, and vascular endothelial phenotypic marker FVIIIRAg. Thus, while collagen V regulates the growth of collagen I fibrils, collagen VI—a connecting protein—links fibrillar collagens to the septal ECM, giving the septa their tensile strength and rigidity. Elastin imparts elasticity to the septa. Collagen IV and laminin support the growth of ductules and venules in the septa.