Immunolocalization of heparinbinding growth factors (HBGF) types 1 and 2 in rat liver. Selective hyperexpression of HBGF‐2 in carbon tetrachloride‐induced fibrosis

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Abstract
Ito cells play a major role in liver fibrosis but the mechanisms controlling their activation in vivo are poorly understood. Heparin‐binding growth factors (H BGF) types 1 and 2 are mitogenic for cultured Ito cells. They have been found in liver extracts but their cellular localization is unknown. We have studied by immunohistochemistry KBGF‐1 and ‐2 expression in normal rat liver and in carbon tetrachloride (CCl4)‐induced fibrosis. In normal liver, HBGF‐1 was present only in sinusoidal cells whereas HBGF‐2 was also detected in endothelial cells lining major vessels. At the acute stage of CC14 intoxication, HBGF‐2 was expressed in centrilobular clusters of mononuclear phagocytes that were surrounded by many HBGF‐2‐negative Ito cells. In the later stages, HBGF‐2 was expressed by Ito cells within the fibrous bands. No modulation of HBGF‐1 expression was noted at any stage. These results suggest that (1) at the acute stage of CC14 intoxication, HBGF‐2 produced by mononuclear phagocytes could participate in the recruitment of Ito cells; and (2) during the CCl4‐induced fibrotic process, HBGF‐2 could contribute to Ito cell proliferation and the synthesis of fibrosis components. In this in vivo model of hepatic fibrosis, the hyperexpression of HBGF‐2 is a relatively specific event since the expression of a structurally related molecule, HBGF‐1 was not modulated.