Rat liver myofibroblasts (MFB) are the key cells involved in the deposition of extracellular matrix in fibrotic liver. They were isolated by repeated passaging of non-parenchymal cell fraction and cultured in 3-dimensional (3D) collagen gel mimicking tissue. The transfer of MFB from plastic dishes to collagen resulted in the change in their shape from large and spread to slender with long extensions. The expression of transforming growth factor-beta1 (TGF-beta1) and of MFB markers, alpha-smooth muscle actin (alpha-SMA) and cellular fibronectin (EDA-FN), on protein level was significantly decreased in collagen gel. The gel did not change the expression of metalloproteinase MMP-2 but activated the proenzyme. The experiments with inhibitors of metabolic pathways showed that EDA-FN and alpha-SMA were differently regulated. The expression of EDA-FN required functional TGF-beta1 receptors and was also dependent on the activity of protein kinases MEK1 and MEK2. alpha-SMA expression was primarily determined by the 3D environment. Fibroblast growth factor-1 (FGF-1) in combination with heparin decreased the expression of alpha-SMA and increased the expression of EDA-FN in the cells on plastic. The cellular environment may influence the cells per se and may modify the action of other agents.

• MeSH
• aktiny metabolismus   MeSH
• benzamidy MeSH
• biologické markery metabolismus   MeSH
• butadieny MeSH
• dioxoly MeSH
• fibroblastový růstový faktor 1 metabolismus   MeSH
• fibronektiny metabolismus   MeSH
• játra cytologie   MeSH
• kultivační techniky * MeSH
• kultivované buňky MeSH
• matrixová metaloproteinasa 2 metabolismus   MeSH
• myofibroblasty cytologie   metabolismus   MeSH
• nitrily MeSH
• potkani Sprague-Dawley MeSH
• transformující růstový faktor beta metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

Acyclic nucleoside phosphonates PMEDAP and PMEG modulate expression of selected proangiogenic genes in SD-lymphoma bearing rats. Antiangiogenic efficacy of PMEDAP is relatively weak and is manifested mainly by down-regulation of vascular endothelial growth factor (VEGF) and its receptor VEGFR detectable 24 hours after treatment. Compound PMEG (an active metabolite of the prodrug GS-9219) down-regulates selected proangiogenic genes EGF, FGF, PDGF, VEGF, EGFR, FGFR, PDGFR and VEGFR much more efficiently. Its antiangiogenic potency persists and is more intensive 48 hours after treatment. Findings show that in vivo antitumour efficacy of both antimitotic acyclic nucleoside phosphonates PMEDAP and PMEG consequently affect the angiogenesis in T-cell lymphoma.

• MeSH
• adenin analogy a deriváty   farmakologie   MeSH
• destičkový růstový faktor genetika   metabolismus   MeSH
• epidermální růstový faktor genetika   metabolismus   MeSH
• erbB receptory genetika   metabolismus   MeSH
• fibroblastový růstový faktor 1 genetika   metabolismus   MeSH
• guanin analogy a deriváty   farmakologie   MeSH
• krysa rodu rattus MeSH
• lymfom T-buněčný genetika   metabolismus   patologie   MeSH
• messenger RNA genetika   metabolismus   MeSH
• organofosforové sloučeniny farmakologie   MeSH
• patologická angiogeneze metabolismus   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• potkani Sprague-Dawley MeSH
• receptor 1 pro vaskulární endoteliální růstový faktor genetika   metabolismus   MeSH
• receptor fibroblastových růstových faktorů, typ 1 genetika   metabolismus   MeSH
• regulace genové exprese u nádorů účinky léků   MeSH
• růstový faktor odvozený z trombocytů - receptor beta genetika   metabolismus   MeSH
• vaskulární endoteliální růstový faktor A genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH