Transforming growth factor-beta 1 stimulates the synthesis of basement membrane proteins laminin, collagen type IV and entactin in rat liver sinusoidal endothelial cells

Background/Aims: It is suggested that during fibrogenesis as well as during carcinogenesis of the liver, the hepatic microvascular phenotype is transf ormed from sinusoids - which lack a basement membrane into continuous capil laries which rest on a basement membrane, As transforming growth factor (TG F)-beta 1 seems to be the most effective mediator in the stimulation of mat rix protein synthesis, we were interested in the modulation of basement mem brane proteins collagen type IV laminin, and entactin expression by TGF-bet a 1 in liver sinusoidal endothelial cells (SECs), especially since a stimul ation 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, lam inin, and collagen type TV and of the extracellular matrix (ECM) proteins t enascin and fibronectin with or without TGF-beta 1 - stimulation was analyz ed 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 isolate d from acutely and chronically CCl4-damaged rat livers and were analyzed fo r matrix protein expression. Results: SECs were adherent 24 h after isolation and formed confluent monol ayers on day 4 of primary culture. Specific immunoprecipitates and specific transcripts for the BM proteins entactin, laminin, and collagen type IV an d for ECM proteins tenascin and fibronectin were detectable in freshly isol ated or cultured SECs. The synthesis of all tested BM proteins and ECM prot eins 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-bet a 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 live r disease.