Gelsolin gene expression is upregulated in damaged rat and human livers within non-parenchymal cells and not in hepatocytes.
Gelsolin, a 90-kDa protein, was suggested to be involved in cell motility, to inhibit apoptosis and to have a protective role for tissue. This study intends to analyse the modulation of cytoplasmic gelsolin expression in damaged rat and human livers and to identify its cellular sources. In the normal liver gelsolin-immunoreactive cells could be identified along vessel walls and along the sinusoids. In cultured rat hepatic stellate cells (HSCs), liver myofibroblasts (MFs), mononuclear cells (MCs) and sinusoidal endothelial cells (SECs), but not in hepatocytes, gelsolin expression could be detected by immunostaining and Northern blot analysis. In acute CCl4-induced liver damage there was no gelsolin positivity detectable in necrotic areas. However, in human fulminant hepatic failure positivity in the necrotic areas was detected. In chronically damaged rat and human livers gelsolin-immunoreactive cells could be identified within the fibrotic septa. Northern blot analysis revealed an increase of the gelsolin-specific transcript level under conditions of acute and chronic human or rat liver damage. The amount of gelsolin-specific transcripts in SECs and large MCs isolated from damaged rat livers increased in comparison to cells obtained from normal rats. However, the amount of gelsolin-specific transcripts in small MCs (representing recruited inflammatory cells) decreased. In conclusion, SECs, MCs, MFs and HSCs, but not hepatocytes, express gelsolin. In the damaged liver all tested cell populations but the inflammatory cells and the hepatocytes are responsible for the enhanced gelsolin expression.
Department of Internal Medicine, Section of Gastroenterology and Endocrinology, Georg-August-University Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany.
Katrin
K
Neubauer
Yacoov
Y
Baruch
Alexander
A
Lindhorst
Bernhard
B
Saile
Giuliano
G
Ramadori
D000818:Animals; D015152:Blotting, Northern; D002908:Chronic Disease; D018260:Gelsolin / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006168:Guinea Pigs; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008107:Liver Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017093:Liver Failure / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015854:Up-Regulation
D018260:Gelsolin; D012333:RNA, Messenger