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Titolo: alpha(2)macroglobulin reduces paracrine and autocrinestimulated matrix synthesis of cultured rat hepatic stellate cells
Autore: Schuftan, GG; Bachem, MG;
 Indirizzi:
 Univ Ulm, Dept Clin Chem & Pathobiochem, D89069 Ulm, Germany Univ Ulm Ulm Germany D89069 n Chem & Pathobiochem, D89069 Ulm, Germany Univ Cologne, Dept Anaesthesiol, D5000 Cologne 41, Germany Univ Cologne Cologne Germany 41 Anaesthesiol, D5000 Cologne 41, Germany
 Titolo Testata:
 EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
fascicolo: 6,
volume: 29,
anno: 1999,
pagine: 519  528
 SICI:
 00142972(199906)29:6<519:ARPAAM>2.0.ZU;25
 Fonte:
 ISI
 Lingua:
 ENG
 Soggetto:
 GROWTHFACTORBETA; FATSTORING CELLS; RECEPTORASSOCIATED PROTEIN; NECROSISFACTORALPHA; LATENT TGFBETA; ITO CELLS; TRANSFORMING GROWTHFACTORBETA1; LIVER FIBROGENESIS; PERISINUSOIDAL LIPOCYTES; EXTRACELLULARMATRIX;
 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, D89070 Ulm, Germany Univ Ulm Klinikum Ulm Germany D89070 m, D89070 Ulm, Germany



 Citazione:
 G.G. Schuftan e M.G. Bachem, "alpha(2)macroglobulin reduces paracrine and autocrinestimulated matrix synthesis of cultured rat hepatic stellate cells", EUR J CL IN, 29(6), 1999, pp. 519528
Abstract
Background Transforming growth factor beta(1) (TGFbeta(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 autocrinestimulated matrix synthesis of cultured rat hepatic stellate cells (HSCs) by scavenging TGFbeta. Methods and results Using native agarose electrophoresis, we demonstrated.that alpha(2)M binds [I125]TGFbeta(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 TGFbeta(1) in these media. As a consequence of TGFbeta scavenging by alpha(2)M, paracrinestimulated 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 autocrinestimulated 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 L1 TGFbeta(1) antisense oligonucleotide to activated HSCs. Conclusion We conclude that alpha(2)M reduces paracrineand autocrinestimulated extracellular matrix synthesis of cultured HSCs by scavenging TGFbeta. 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