title: Response of Hepatic Stellate Cells to TGFB1 Differs from the Response of Myofibroblasts. Decorin Protects against the Action of Growth Factor.
abstract: Regardless to the exact nature of damage, hepatic stellate cells (HSCs) and other non-parenchymal liver cells transform to activated myofibroblasts, synthesizing the accumulating extracellular matrix (ECM) proteins, and transforming growth factor-β1 (TGF-β1) plays a crucial role in this process. Later it was discovered that decorin, member of the small leucin rich proteoglycan family is able to inhibit this action of TGF-β1. The aim of our present study was to clarify whether HSCs and activated myofibroblasts of portal region exert identical or different response to TGF-β1 exposure, and the inhibitory action of decorin against the growth factor is a generalized phenomenon on myofibroblast of different origin? To this end we measured mRNA expression and production of major collagen components (collagen type I, III and IV) of the liver after stimulation and co-stimulation with TGF-β1 and decorin in primary cell cultures of HSCs and myofibroblasts (MFs). Production of matrix proteins, decorin and members of the TGF-β1 signaling pathways were assessed on Western blots. Messenger RNA expression of collagens and TIEG was quantified by real-time RT-PCR. HSCs and MFs responded differently to TGF-β1 exposure. In contrast to HSCs in which TGF-β1 stimulated the synthesis of collagen type I, type III, and type IV, only the increase of collagen type IV was detected in portal MFs. However, in a combined treatment, decorin seemed to interfere with TGF-β1 and its stimulatory effect was abolished. The different mode of TGF-β1 action is mirrored by the different activation of signaling pathways in activated HSCs and portal fibroblasts. In HSCs the activation of pSMAD2 whereas in myofibroblasts the activation of MAPK pathway was detected. The inhibitory effect of decorin was neither related to the Smad-dependent nor to the Smad-independent signaling pathways.
authors: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, Budapest, H-1085, Hungary.
authors: Alexandra
authors: A
authors: Fullár
authors: 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors: Gábor
authors: G
authors: Firneisz
authors: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, Budapest, H-1085, Hungary.
authors: Eszter
authors: E
authors: Regős
authors: Department of Otorhinolaryngology, Medical University Innsbruck, Innsbruck, Austria.|Department of Gastroenterology and Endocrinology, George August University, Göttingen, Germany.
authors: József
authors: J
authors: Dudás
authors: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, Budapest, H-1085, Hungary.
authors: Tibor
authors: T
authors: Szarvas
authors: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, Budapest, H-1085, Hungary.
authors: Kornélia
authors: K
authors: Baghy
authors: Department of Gastroenterology and Endocrinology, George August University, Göttingen, Germany.
authors: Giuliano
authors: G
authors: Ramadori
authors: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, Budapest, H-1085, Hungary. koval@korb1.sote.hu.
authors: Ilona
authors: http://orcid.org/0000-0002-0179-3378
authors: I
authors: Kovalszky
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D058575:Decorin / Q000494:pharmacology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D058628:Myofibroblasts / Q000187:drug effects* / Q000378:metabolism*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D058575:Decorin; D016326:Extracellular Matrix Proteins; D036341:Intercellular Signaling Peptides and Proteins; D020011:Protective Agents; D053773:Transforming Growth Factor beta1; D003094:Collagen
keywords: Decorin; HSC; Hepatic fibrosis; Myofibroblast; TGF-β signaling