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Hepatic stellate cell – vitamin A-rich cells
Quiescent hepatic stellate cells (HSCs) are characterized by their localization of perisinusoidal cells and their long cytoplasmic processes, extending both along and around the sinusoids as well as between the hepatocytes. These long cytoplasmic processes, which have numerous vitamin A-containing lipid droplets, are essential for the identification of HSCs in the quiescent phase. Glial fibrillary acidic protein (GFAP) (Abcam, Cambridge, UK) is another crucial marker for HSCs which may allow a distinction to be made between the HSCs and other fibroblastic liver cells. However, induction of alpha-smooth muscle actin (α-SMA) is the most reliable marker of stellate cell activation because it is absent from other resident hepatocytes in a normal or injured liver, with the exception of the smooth muscle cells surrounding large vessels where it is present. Desmin has been used as a typical marker for contractile stellate cells in rodent livers; however, its expression is unreliable in humans. Furthermore, HSCs’ transdifferentiation to the active phase has been proven to rely on E-cadherin switching to N-cadherin during HSC activation. Significant evidence now exists to consider HSCs as the main matrix-producing cells in the process of the liver fibrosis. Liver injury, regardless of the aetiology, tumour growth and metastases will ultimately lead to activation of HSCs. Several studies have dissected the molecular mechanisms involved in liver fibrosis, most of which are intimately connected to HSCs. As a result, a number of key steps in the process of stellate cell activation and fibrogenesis have been identified as potential therapeutic targets that may be clinically useful in preventing, or treating, liver fibrosis.