Vitamin A‐Storing Cells (Stellate Cells)

Abstract

Hepatic stellate cells (HSCs; also called as vitamin A-storing cells, lipocytes, interstitial cells, fat-storing cells, Ito cells) exist in the space between parenchymal cells and sinusoidal endothelial cells of the hepatic lobule, and store 80% of vitamin A in the whole body as retinyl palmitate in lipid droplets in the cytoplasm. In physiological conditions, these cells play pivotal roles in the regulation of vitamin A 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. HSCs in Arctic animals such as polar bears and Arctic foxes store 20-100 times the levels of vitamin A found in human or rat. HSCs play an important role in the liver regeneration. A gradient of vitamin A-storage capacity exists among the SCs in a hepatic lobule. The gradient was expressed as a symmetrical biphasic distribution starting at the periportal zone, peaking at the middle zone, and sloping down toward the central zone in the hepatic lobule. In pathological conditions such as liver fibrosis, HSCs lose vitamin A and synthesize a large amount of extracellular matrix (ECM) components including collagen, proteoglycan, and adhesive glycoproteins. Morphology of these cells also changes from the star-shaped SCs to that of fibroblasts or myofibroblasts. The three-dimensional structure of ECM components was found to regulate reversibly the morphology, proliferation, and functions of the HSCs. Molecular mechanisms in the reversible regulation of the SCs by ECM imply cell surface integrin-binding to ECM components followed by signal transduction processes and then cytoskeleton assembly. SCs also exist in extrahepatic organs such as pancreas, lung, kidney, and intestine. Hepatic and extrahepatic SCs form the SC system.