Fibrogenesis in acute liver injuries.
We describe changes in the hepatic extracellular matrix (ECM) and its producing cells in acute liver injuries, primarily referring to transforming growth factor-beta 1 (TGF-beta), which is the most important cytokine involved in fibrogenesis. In addition, we describe the relationship between vitronectin (VN) and plasminogen activator inhibitor 1(PAI-1) in the self regulating mechanism of TGF-beta action for fibrogenesis in acute viral hepatitis. In the very early stage of acute liver injury, following aggregation of platelets, immunolocalization of TGF-beta is observed in injured areas. And at the cell migration stage, the infiltration pattern of inflammatory cells was characterized by an ordered progression of inflammatory cells, beginning with platelets and followed by polymorphonuclear leukocytes and macrophages. Following recruitment of inflammatory cells to the necrotic area, it appears that TGF-beta could be produced and activated by these inflammatory cells, resulting in the intensification of active TGF-beta distributions in the injured area. At the fibrosis stage, TGF-beta could also be produced by Ito cells, endothelial cells and hepatocytes at the periphery of the necrotic area, and may play important roles in the promotion of production and accumulation of ECM components in injured regions. In addition, the consistent localization of PAI-1 with VN in ECM near the necroinflammatory areas suggests that PAI-1 and VN could be involved in the modulation of fibrogenesis in acute liver injuries. In many kinds of acute liver injuries, fibrogenesis is usually considered to be transient, and injured liver tissues able to nearly recover in order.(ABSTRACT TRUNCATED AT 250 WORDS)
Inuzuka
S
S
Second Department of Medicine, Kurume University, School of Medicine, Japan.
Ueno
T
T
Tanikawa
K
K
D000818:Animals; D005355:Fibrosis / Q000503:physiopathology; D006801:Humans; D008099:Liver / Q000293:injuries* / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000502:physiology
D016212:Transforming Growth Factor beta