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Transforming growth factor-beta 1 stimulates the synthesis of basement membrane proteins laminin, collagen type IV and entactin in rat liver sinusoidal endothelial cells
Author(s): Neubauer K, Kruger M, Quondamatteo F, Knittel T, Saile B, Ramadori G
Source: JOURNAL OF HEPATOLOGY    Volume: 31    Issue: 4    Pages: 692-702    Published: OCT 1999  
Times Cited: 28     References: 54     
Abstract: Background/Aims: It is suggested that during fibrogenesis as well as during carcinogenesis of the liver, the hepatic microvascular phenotype is transformed from sinusoids - which lack a basement membrane into continuous capillaries which rest on a basement membrane, As transforming growth factor (TGF)-beta 1 seems to be the most effective mediator in the stimulation of matrix protein synthesis, we were interested in the modulation of basement membrane proteins collagen type IV laminin, and entactin expression by TGF-beta 1 in liver sinusoidal endothelial cells (SECs), especially since a stimulation of the synthesis of collagen type TV but not of entactin and laminin by TGF-beta 1 has been demonstrated in a fibrosarcoma cell line.

Methods: The synthesis of the basement membrane (BM) proteins entactin, laminin, and collagen type TV and of the extracellular matrix (ECM) proteins tenascin and fibronectin with or without TGF-beta 1 - stimulation was analyzed by immunostaining, immunoprecipitation of endogenously labeled proteins and Northern blot analysis of total RNA extracted from freshly isolated or cultured SECs from rat or guinea pig livers. Furthermore, SECs were isolated from acutely and chronically CCl4-damaged rat livers and were analyzed for matrix protein expression.

Results: SECs were adherent 24 h after isolation and formed confluent monolayers on day 4 of primary culture. Specific immunoprecipitates and specific transcripts for the BM proteins entactin, laminin, and collagen type IV and for ECM proteins tenascin and fibronectin were detectable in freshly isolated or cultured SECs. The synthesis of all tested BM proteins and ECM proteins was stimulated at least 3-fold by TGF-PL. In SECs isolated after CCl4-induced acute and chronic liver damage, increased levels of matrix protein transcripts were detectable.

Conclusions: The stimulation of the synthesis of all BM-proteins by TGF-beta 1 in vitro and the accumulation of ECM transcripts in SECs isolated from CCl4-treated livers, suggests that SECs are involved in the formation of a basement membrane during the "capillarization" of the sinusoids during liver disease.

Document Type: Article
Language: English
Reprint Address: Ramadori, G (reprint author), Univ Gottingen, Sect Gastroenterol & Endocrinol, Dept Internal Med, Robert Koch Str 40, D-37075 Gottingen, Germany
Addresses:
1. Univ Gottingen, Sect Gastroenterol & Endocrinol, Dept Internal Med, D-37075 Gottingen, Germany
2. Univ Gottingen, Dept Histol, D-37075 Gottingen, Germany
Publisher: MUNKSGAARD INT PUBL LTD, 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK
Subject Category: Gastroenterology & Hepatology
IDS Number: 247HX
ISSN: 0168-8278
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