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Titolo:
alpha(2)-macroglobulin reduces paracrine- and autocrine-stimulated matrix synthesis of cultured rat hepatic stellate cells
Autore:
Schuftan, GG; Bachem, MG;
Indirizzi:
Univ Ulm, Dept Clin Chem & Pathobiochem, D-89069 Ulm, Germany Univ Ulm Ulm Germany D-89069 n Chem & Pathobiochem, D-89069 Ulm, Germany Univ Cologne, Dept Anaesthesiol, D-5000 Cologne 41, Germany Univ Cologne Cologne Germany 41 Anaesthesiol, D-5000 Cologne 41, Germany
Titolo Testata:
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
fascicolo: 6, volume: 29, anno: 1999,
pagine: 519 - 528
SICI:
0014-2972(199906)29:6<519:ARPAAM>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
GROWTH-FACTOR-BETA; FAT-STORING CELLS; RECEPTOR-ASSOCIATED PROTEIN; NECROSIS-FACTOR-ALPHA; LATENT TGF-BETA; ITO CELLS; TRANSFORMING GROWTH-FACTOR-BETA-1; LIVER FIBROGENESIS; PERISINUSOIDAL LIPOCYTES; EXTRACELLULAR-MATRIX;
Keywords:
alpha(2)-macroglobulin; hepatic stellate cells; fibrogenesis; transforming growth factor beta;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
53
Recensione:
Indirizzi per estratti:
Indirizzo: Bachem, MG Univ Ulm Klinikum, Inst Klin Chem, D-89070 Ulm, Germany Univ Ulm Klinikum Ulm Germany D-89070 m, D-89070 Ulm, Germany
Citazione:
G.G. Schuftan e M.G. Bachem, "alpha(2)-macroglobulin reduces paracrine- and autocrine-stimulated matrix synthesis of cultured rat hepatic stellate cells", EUR J CL IN, 29(6), 1999, pp. 519-528

Abstract

Background Transforming growth factor beta(1) (TGF-beta(1)) is considered to represent a major fibrogenic mediator in the liver. The aim of the present study was to investigate whether alpha(2)-macroglobulin (alpha(2)M) might reduce paracrine- and autocrine-stimulated matrix synthesis of cultured rat hepatic stellate cells (HSCs) by scavenging TGF-beta. Methods and results Using native agarose electrophoresis, we demonstrated.that alpha(2)M binds [I-125]-TGF-beta(1) within minutes. Preincubation of transiently acidified supernatants of cultured Kupffer cells, secondary cultured (activated) HSC and platelet lysate with, respectively, 500 and 2000 mu g mL(-1) alpha(2)M significantly reduced the concentration of active TGF-beta(1) in these media. As a consequence of TGF-beta scavenging by alpha(2)M, paracrine-stimulated proteoglycan synthesis of primary cultured HSCs was reduced significantly. Furthermore, addition of 200 mu g mL(-1) alpha(2)Mto passaged (activated) HSCs resulted in (a) a reduction in autocrine-stimulated extracellular matrix synthesis (proteoglycan -52%, fibronectin -55%)and (b) increased cell proliferation. A similar reduction in matrix synthesis was observed after the addition of 5 mu mol L-1 TGF-beta(1) antisense oligonucleotide to activated HSCs. Conclusion We conclude that alpha(2)M reduces paracrine-and autocrine-stimulated extracellular matrix synthesis of cultured HSCs by scavenging TGF-beta. These mechanisms might restrict liver fibrogenesis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/07/20 alle ore 14:17:44