Fig. (1). Fiborsis development. Sinusoidal events during fibrosing liver injury. Changes in the subendothelial space of Disse and sinusoid as fibrosis develops in response to liver injury include alterations in both cellular responses and extracellular matrix composition. Stellate cell activation leads to accumulation of scar (fibril-forming) matrix. This in turn contributes to the loss of hepatocyte microvilli and sinusoidal endothelial fenestrae, which result in deterioration of hepatic function. Kupffer cell(macrophage) activation accompanies liver injury and contributes to paracrine activation of stellate cells (as in Friedman SL. J Biol Chem 2000 Jan 28;275(4):2247-50 Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury).