Heparan sulfate proteoglycan expression in normal human liver

Because increasing evidence implicates heparan sulfate proteoglycans (HSPGs) as essential cofactors in receptor‐growth factor interactions, in cell‐cell recognition systems, and in cell‐matrix adhesion processes and yet little is known about their cellular distribution pattern and cellular sources in liver tissue, we used monoclonal antibodies specific for the core proteins of syndecan1, 2, 3, 4, glypican, and perlecan to investigate their immunohistochemical expression in normal adult human liver biopsy specimens. Syndecan1 was expressed in sinusoidal endothelial cells, whereas the endothelium of the portal tract vessels was negative. Hepatocytes showed a membranous staining pattern of the sinusoidal and intercellular domain. Bile duct epithelial cells showed basolateral membrane positivity. Immunoreactivity for syndecan2 was seen in mesenchymal cells, accentuated around bile ducts. Syndecan3 showed intense staining of hepatic arterial and portal venous endothelial cells, of mesenchymal cells, and of Ito cells. Immunohistochemistry for syndecan4 showed a granular staining pattern of hepatocytes at their bile canalicular pole. Glypican showed weak positivity in portal tract mesenchymal cells and clear positivity in nerve bundles. Perlecan was present in Disse's space, in endothelial cells, in basement membranes surrounding bile ducts and vessels, in vessel walls, and in mesenchymal cells. The highly differential expression of these HSPGs in the different cell compartments of the liver, as well as in basement membranes and in Disse's space, suggests that each of these proteoglycans has a specific function in the interplay of cells, matrix molecules, growth factors, and proteinases.(HEPATOLOGY 1995; 21:950–958.)

[1]  J. Scoazec,et al.  Endothelial cell heterogeneity in the normal human liver acinus: in situ immunohistochemical demonstration. , 2008, Liver.

[2]  G. David.  Integral membrane heparan sulfate proteoglycans , 1993, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[3]  A. Mallat,et al.  Mitogenic effect of transforming growth factor‐β1 on human ito cells in culture: Evidence for mediation by endogenous platelet‐derived growth factor , 1993, Hepatology.

[4]  D. Dhumeaux,et al.  Immunolocalization of heparinbinding growth factors (HBGF) types 1 and 2 in rat liver. Selective hyperexpression of HBGF‐2 in carbon tetrachloride‐induced fibrosis , 1993, The Journal of pathology.

[5]  N. Yamamoto,et al.  Stimulation of DNA synthesis in hepatocytes by hepatocyte growth factor bound to extracellular matrix. , 1993, Biochemical and biophysical research communications.

[6]  D. Moscatelli,et al.  Basic fibroblast growth factor is internalized through both receptor-mediated and heparan sulfate-mediated mechanisms. , 1992, The Journal of biological chemistry.

[7]  X. Bai,et al.  Developmental changes in heparan sulfate expression: in situ detection with mAbs , 1992, The Journal of cell biology.

[8]  J. Cassiman,et al.  Cell surface heparan sulfate proteoglycans from human vascular endothelial cells. Core protein characterization and antithrombin III binding properties. , 1992, The Journal of biological chemistry.

[9]  D. Rifkin,et al.  The extracellular regulation of growth factor action. , 1992, Molecular biology of the cell.

[10]  E. Edelman,et al.  Kinetics of basic fibroblast growth factor binding to its receptor and heparan sulfate proteoglycan: a mechanism for cooperactivity. , 1992, Biochemistry.

[11]  P. Marynen,et al.  Molecular cloning of amphiglycan, a novel integral membrane heparan sulfate proteoglycan expressed by epithelial and fibroblastic cells , 1992, The Journal of cell biology.

[12]  L. Reid,et al.  The liver as a stem cell and lineage system. , 1992, The American journal of physiology.

[13]  J. Marcum,et al.  Isolation and characterization of heparan sulfate proteoglycans produced by cloned rat microvascular endothelial cells. , 1992, The Journal of biological chemistry.

[14]  J. Cassiman,et al.  Differential expression of cell surface heparan sulfate proteoglycans in human mammary epithelial cells and lung fibroblasts. , 1992, The Journal of biological chemistry.

[15]  J G Flanagan,et al.  Heparin is required for cell-free binding of basic fibroblast growth factor to a soluble receptor and for mitogenesis in whole cells , 1992, Molecular and cellular biology.

[16]  M. Sporn,et al.  Cytokines in context , 1991, The Journal of cell biology.

[17]  K. Sakaguchi,et al.  Identification of heparan sulfate proteoglycan as a high affinity receptor for acidic fibroblast growth factor (aFGF) in a parathyroid cell line. , 1991, Journal of Biological Chemistry.

[18]  Jeffrey D. Esko,et al.  Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor , 1991, Cell.

[19]  P. Marynen,et al.  Molecular cloning of a phosphatidylinositol-anchored membrane heparan sulfate proteoglycan from human lung fibroblasts , 1990, The Journal of cell biology.

[20]  M. Goldfarb.  The fibroblast growth factor family. , 1990, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[21]  J. Cassiman,et al.  The core protein of the matrix-associated heparan sulfate proteoglycan binds to fibronectin. , 1990, The Journal of biological chemistry.

[22]  G. Michalopoulos,et al.  Acidic fibroblast growth factor (HBGF‐1) stimulates DNA synthesis in primary rat hepatocyte cultures , 1990, Journal of cellular physiology.

[23]  L. Gesualdo,et al.  Effects of platelet-derived growth factor and other polypeptide mitogens on DNA synthesis and growth of cultured rat liver fat-storing cells. , 1989, The Journal of clinical investigation.

[24]  M. Paulsson,et al.  Matrix-associated heparan sulfate proteoglycan: core protein-specific monoclonal antibodies decorate the pericellular matrix of connective tissue cells and the stromal side of basement membranes , 1989, The Journal of cell biology.

[25]  I. Thesleff,et al.  Syndecan from embryonic tooth mesenchyme binds tenascin. , 1989, The Journal of biological chemistry.

[26]  B. Clement,et al.  Identification of a cell surface-binding protein for the core protein of the basement membrane proteoglycan. , 1989, The Journal of biological chemistry.

[27]  J. Cassiman,et al.  Multiple distinct membrane heparan sulfate proteoglycans in human lung fibroblasts. , 1989, The Journal of biological chemistry.

[28]  M. Jalkanen,et al.  Molecular cloning of syndecan, an integral membrane proteoglycan , 1989, The Journal of cell biology.

[29]  D. Mosher,et al.  Heparan sulfate-mediated binding of epithelial cell surface proteoglycan to thrombospondin. , 1989, The Journal of biological chemistry.

[30]  M. Bernfield,et al.  Cell surface proteoglycan binds mouse mammary epithelial cells to fibronectin and behaves as a receptor for interstitial matrix , 1988, The Journal of cell biology.

[31]  M. Jalkanen,et al.  Immunocytochemistry of cell surface heparan sulfate proteoglycan in mouse tissues. A light and electron microscopic study. , 1987, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[32]  R. Mecham,et al.  Biology of Proteoglycans , 1987 .

[33]  G. Laurie,et al.  Localization of binding sites for laminin, heparan sulfate proteoglycan and fibronectin on basement membrane (type IV) collagen. , 1986, Journal of molecular biology.

[34]  J. J. van den Oord,et al.  A recommended procedure for ultrastructural immunohistochemistry on small human tissue samples. , 1985, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[35]  M. Bernfield,et al.  Heparan sulfate proteoglycans from mouse mammary epithelial cells. Basal extracellular proteoglycan binds specifically to native type I collagen fibrils. , 1984, The Journal of biological chemistry.

[36]  E. Nardin,et al.  Inhibition of entry of Plasmodium falciparum and P. vivax sporozoites into cultured cells; an in vitro assay of protective antibodies. , 1984, Journal of immunology.

[37]  M. Hollingdale,et al.  Entry of Plasmodium berghei sporozoites into cultured cells, and their transformation into trophozoites. , 1983, The American journal of tropical medicine and hygiene.

[38]  A. Guillouzo,et al.  Distribution and origin of the basement membrane component perlecan in rat liver and primary hepatocyte culture. , 1993, The American journal of pathology.

[39]  J. Spring,et al.  Biology of the syndecans: a family of transmembrane heparan sulfate proteoglycans. , 1992, Annual review of cell biology.

[40]  L. Kjellén,et al.  Proteoglycans: structures and interactions. , 1991, Annual review of biochemistry.

[41]  T. Maciag,et al.  The heparin-binding (fibroblast) growth factor family of proteins. , 1989, Annual review of biochemistry.

[42]  M. Klagsbrun.  The fibroblast growth factor family: structural and biological properties. , 1989, Progress in growth factor research.

[43]  A. Rapraeger.  Integral Membrane Proteoglycans as Matrix Receptors: Role in Cytoskeleton and Matrix Assembly at the Epithelial Cell Surface , 1987 .