Biomaterial Database

Contribution of sinusoidal endothelial liver cells to liver fibrosis: expression of transforming growth factor-beta 1 receptors and modulation of plasmin-generating enzymes by transforming growth factor-beta 1. 1993

H Rieder, and T Armbrust, and K H Meyer zum Büschenfelde, and G Ramadori

I. Medizinische Klinik und Poliklinik, Johannes-Gutenberg Universität Mainz, Germany.

Transforming growth factor-beta 1 is an important cytokine in the pathophysiology of liver fibrosis, stimulating the production of extracellular matrix. Whether this cytokine can also control the degradation of matrix proteins in liver cells has not been investigated. Because plasmin is an important protease for the degradation of matrix glycoproteins, we investigated whether sinusoidal endothelial liver cells could contribute to fibrosing liver disease through the modulation of plasmin-generating enzymes in response to transforming growth factor-beta 1. Sinusoidal endothelial cells from guinea pig liver were investigated in pure monolayer culture. Using 125I-labelled transforming growth factor-beta, we demonstrated high-affinity binding sites on sinusoidal endothelial cells at a density of 9.3 x 10(2) per cell, and a dissociation constant of about 5.5 x 10(-11) mol/L. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed the known three classes of membrane receptors for transforming growth factor-beta. Using biosynthetic labeling of proteins with 35S-methionine, immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, we showed that sinusoidal endothelial cells produce and secrete plasminogen activator inhibitor type 1 from the beginning of culture. Treatment of confluent cell cultures for 24 hr with transforming growth factor-beta 1 increased synthesis and release of plasminogen activator inhibitor type 1. The response was almost maximal at a concentration of 1 ng transforming growth factor-beta/ml and paralleled the increased synthesis of fibronectin. On reverse fibrin autography we proved that transforming growth factor-beta 1 stimulated the release of functionally active plasminogen activator inhibitor type 1.(ABSTRACT TRUNCATED AT 250 WORDS)

UI	MeSH Term	Description	Entries
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008106	Liver Cirrhosis, Experimental	Experimentally induced chronic injuries to the parenchymal cells in the liver to achieve a model for LIVER CIRRHOSIS.	Hepatic Cirrhosis, Experimental,Cirrhoses, Experimental Liver,Cirrhosis, Experimental Liver,Experimental Liver Cirrhoses,Experimental Liver Cirrhosis,Liver Cirrhoses, Experimental,Experimental Hepatic Cirrhosis
D010960	Plasminogen Activators	A heterogeneous group of proteolytic enzymes that convert PLASMINOGEN to FIBRINOLYSIN. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation.	Extrinsic Plasminogen Activators,Plasminogen Activator,Uterine-Tissue Plasminogen Activator,Uterine Tissue Plasminogen Activator
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D004730	Endothelium, Vascular	Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.	Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D005260	Female		Females
D005341	Fibrinolysin	A product of the lysis of plasminogen (profibrinolysin) by PLASMINOGEN activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins.	Plasmin,Fibrogammin,Glu-Plasmin,Protease F,Thrombolysin,Glu Plasmin
D006168	Guinea Pigs	A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.	Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D016212	Transforming Growth Factor beta	A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.	Bone-Derived Transforming Growth Factor,Platelet Transforming Growth Factor,TGF-beta,Milk Growth Factor,TGFbeta,Bone Derived Transforming Growth Factor,Factor, Milk Growth,Growth Factor, Milk