Molecular mechanisms in the reversible regulation of morphology, proliferation and collagen metabolism in hepatic stellate cells by the three-dimensional structure of the extracellular matrix.

Hepatic stellate cells (vitamin A-storing cells, lipocytes, interstitial cells, fat-storing cells, Ito cells) exist in the perisinusoidal space of the hepatic lobule and store 80% of the body's retinoids as retinyl palmitate in lipid droplets in the cytoplasm. Under physiological conditions, these cells play pivotal roles in the regulation of retinoid homeostasis; they express specific receptors for retinol-binding protein (RBP), a binding protein specific for retinol, on their cell surface, and take up the complex of retinol and RBP by receptor-mediated endocytosis. However, in pathological conditions such as liver fibrosis, these cells lose retinoids and synthesize a large amount of extracellular matrix (ECM) components including collagen, proteoglycan and adhesive glycoproteins. The morphology of these cells also changes from star-shaped stellate cells to that of fibroblasts or myofibroblasts. The three-dimensional structure of ECM components was found to regulate reversibly the morphology, proliferation and functions of hepatic stellate cells. Molecular mechanisms in the reversible regulation of stellate cells by ECM imply cell surface integrin binding to ECM components followed by signal transduction processes and then cytoskeleton assembly.