Immunolocalization of heparin-binding growth factors (HBGF) types 1 and 2 in rat liver. Selective hyperexpression of HBGF-2 in carbon tetrachloride-induced fibrosis.
Ito cells play a major role in liver fibrosis but the mechanisms controlling their activation in vivo are poorly understood. Heparin-binding growth factors (HBGF) 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 HBGF-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 CCl4 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 CCl4 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.
Charlotte
F
F
Unité INSERM 99, Créteil, France.
Win
K M
KM
Preaux
A M
AM
Mavier
P
P
Dhumeaux
D
D
Zafrani
E S
ES
Rosenbaum
J
J
D000818:Animals; D002251:Carbon Tetrachloride; D016220:Fibroblast Growth Factor 1 / Q000032:analysis; D016222:Fibroblast Growth Factor 2 / Q000032:analysis; D005346:Fibroblast Growth Factors / Q000032:analysis*; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry* / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D005346:Fibroblast Growth Factors; D002251:Carbon Tetrachloride