Adhesion between Cells and Extracellular Matrix with Special Reference to Hepatic Stellate Cell Adhesion to Three-dimensional Collagen Fibers.

Abstract

ABSTRACT. Hepatic stellate cells are located in the perisinusoidal space (space of Disse), and extend their dendritic, thin membranous processes and fine fibrillar processes into this space. The stellate cells coexist with a three-dimensional extracellular matrix (ECM) in the perisinusoidal space. In turn the three-dimensional structure of the ECM regulates the proliferation, morphology, and functions of the stellate cell. In this review, the morphology of sites of adhesion between hepatic stellate cells and extracellular matrix is described. Hepatic stellate cells cultured in polystyrene dishes spread well, whereas the cells cultured on or in type I collagen gel become slender and elongate their long cellular processes which adhere directly to the collagen fibers. Cells in type I collagen gel form a large number of adhesive structures, each adhesive area forming a face but not a point. Adhesion molecules, integrins, for the ECM are localized on the cell surface. Elongation of the cellular processes occurs via integrin-binding to type I collagen fibers. The signal transduction mechanism, including protein and phosphatidylinositol phosphorylation, is critical to induce and sustain the cellular processes. Information on the three-dimensional structures of ECM is transmitted via three-dimensional adhesive structures containing the integrins.Key words: hepatic stellate cells/extracellular matrix/cell-extracellular matrix adhesion/type I collagen/three-dimensional structureThe extracellular matrix (ECM) is known to regulate a diversity of biological activities, including cell proliferation, differentiation, migration, polarity, tumorigenesis and cancer metastasis. The cells adhere to ECM by specialized cellular devices such as focal contacts, podosomes, point contacts, and hemidesmosomes (Senoo and Hata, 1994b).The ECM is composed of an insoluble complex of collagens, adhesive glycoproteins (e.g., fibronectin, laminin), proteoglycans (PGs) (e.g., heparan sulfate PGs, chondroitin sulfate PGs) and elastin. These ECM components construct an insoluble supramolecular complex (reviewed by Hata, 1996), the molecules of which contain positional information relayed back as signals to the cells that produce them or to neighboring cells, as well as regulate their growth and metabolism (reviewed by Hata, 1996).Integrins are the major family of cell surface receptors that mediate attachment to the ECM (Hynes, 1992;Clark and Brugge, 1995;Giancotti and Ruoslahti, 1999). Formation of focal contacts is regulated by intracellular signals which promote integrin clustering and cytoskeletal associations. The relationship between the cells and ECM is one of the most important aspects with regard to the nature of the cells.Hepatic stellate cells (vitamin A-storing cells, lipocytes, fat-storing cells) lie in the perisinusoidal space (space of Disse) (Wake, 1980(Wake, , 1995(Wake, , 1997 and coexist with the threedimensional ECM components within the space. The types of ECM components regulate the behavior of the stellate cell (Senoo et al.,...

Effect of Collagen I Gel on Apoptosis of Rat Hepatic Stellate Cells

“…Total viable cell number is much lower when dermal fibroblasts are cultured within low density (0.66%) collagen gel than in high density (3-5%) gel (9). Cell adhesion to collagen fibres is mediated by integrins (10). Integrins α v β 3 were shown to be involved in the regulation of HSC proliferation and apoptosis (27).…”

Cell?cell junctions between mammalian (human and rat) hepatic stellate cells

“…The stellate cells are the main storage sites for vitamin A in the liver (Wake 1971;Senoo and Wake 1985;Hendriks et al 1985;Elhanany et al 1986;Brouwer et al 1988;Blomhoff et al 1990). Hepatic stellate cells are located between characteristic fenestrated sinusoidal endothelial cells (Wisse 1970;Braet and Wisse 2002) and parenchymal cells in the hepatic lobules (Wake 1980(Wake , 1997Brouwer et al 1988;Imai et al 2000aImai et al , 2000b. Thorn-like microprojections of the cytoplasmic processes of the stellate cells make contact with the plasma membrane of the parenchymal cells (Wake 1995), and these cell-cell contacts participate in the organization of the cells in the wall of the hepatic sinusoid.…”

“…Moreover, the structural organization of tissues is known to be regulated not only by cell-cell interactions, but also by cell-extracellular matrix (ECM) interactions (Horwitz and Werb 1998;Imai et al 2000b). ECM components such as type I and III collagen and fibronectin construct a three-dimensional insoluble supramolecular complex; ECM regulates cell growth, metabolism, and morphogenesis through cell-surface receptors such as the integrins (Geerts et al 1985;Hata 1996Hata , 1998Imai and Senoo 1998;Sato and Senoo 1998;Imai et al 2000b).…”

“…ECM components such as type I and III collagen and fibronectin construct a three-dimensional insoluble supramolecular complex; ECM regulates cell growth, metabolism, and morphogenesis through cell-surface receptors such as the integrins (Geerts et al 1985;Hata 1996Hata , 1998Imai and Senoo 1998;Sato and Senoo 1998;Imai et al 2000b). The long-acting vitamin C derivative, L-ascorbic acid 2-phosphate (Asc 2-P), stimulates collagen synthesis, accumulation of collagen fibers, and tissue formation of cultured cells Senoo et al 1989).…”

Vitamin A storage in hepatic stellate cells in the regenerating rat liver: With special reference to zonal heterogeneity

“…Hepatic stellate cells (HSCs; also called vitamin A-storing cells, fat-storing cells, lipocytes, and interstitial cells) are located in the perisinusoidal space of Disse and extend their thin fibrillar processes into this space (Wake, 1971(Wake, , 1980Senoo, 1998, 2000;Imai et al, 2000a). Under physiological conditions, the HSCs store about 80% of the total vitamin A in the whole body as retinyl esters in lipid droplets in their cytoplasm, and they show heterogeneity in their vitamin A-storing capacity within the liver lobules (Wake and Sato, 1993;Zou et al, 1998).…”