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.,...