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Pathology & Oncology Research

, Volume 23, Issue 2, pp 287–294 | Cite as

Response of Hepatic Stellate Cells to TGFB1 Differs from the Response of Myofibroblasts. Decorin Protects against the Action of Growth Factor

  • Alexandra Fullár
  • Gábor Firneisz
  • Eszter Regős
  • József Dudás
  • Tibor Szarvas
  • Kornélia Baghy
  • Giuliano Ramadori
  • Ilona KovalszkyEmail author
Original Article

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.

Keywords

Hepatic fibrosis HSC Myofibroblast Decorin TGF-β signaling 

Notes

Acknowledgments

This study was supported by the National Scientific Found (OTKA) 67925 and 100904, OM-8/2004 grants, by the Székelyhidi Miklós. Award of the Hungarian Liver Research Foundation, by the European Community Action Schemes for the Mobility of University Students (ERASMUS), and the DAAD/MÖB 2007/25 fellowship, NTP-FÖ-P-15-0903.

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Copyright information

© Arányi Lajos Foundation 2016

Authors and Affiliations

  1. 1.1st Department of Pathology and Experimental Cancer ResearchSemmelweis UniversityBudapestHungary
  2. 2.2nd Department of Internal MedicineSemmelweis UniversityBudapestHungary
  3. 3.Department of OtorhinolaryngologyMedical University InnsbruckInnsbruckAustria
  4. 4.Department of Gastroenterology and EndocrinologyGeorge August UniversityGöttingenGermany

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