Lucia Wickert
RWTH Aachen University
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Publication
Featured researches published by Lucia Wickert.
Hepatology | 2006
Eliza Wiercinska; Lucia Wickert; Bernd Denecke; Harun M. Said; Jafar Hamzavi; Axel M. Gressner; Midori Thorikay; Peter ten Dijke; Peter R. Mertens; Katja Breitkopf; Steven Dooley
Transforming growth factor (TGF)‐β is critically involved in the activation of hepatic stellate cells (HSCs) that occurs during the process of liver damage, for example, by alcohol, hepatotoxic viruses, or aflatoxins. Overexpression of the TGF‐β antagonist Smad7 inhibits transdifferentiation and arrests HSCs in a quiescent stage. Additionally, bile duct ligation (BDL)‐induced fibrosis is ameliorated by introducing adenoviruses expressing Smad7 with down‐regulated collagen and α‐smooth muscle actin (α‐SMA) expression. The aim of this study was to further characterize the molecular details of TGF‐β pathways that control the transdifferentiation process. In an attempt to elucidate TGF‐β target genes responsible for fibrogenesis, an analysis of Smad7‐dependent mRNA expression profiles in HSCs was performed, resulting in the identification of the inhibitor of differentiation 1 (Id1) gene. Ectopic Smad7 expression in HSCs strongly reduced Id1 mRNA and protein expression. Conversely, Id1 overexpression in HSCs enhanced cell activation and circumvented Smad7‐dependent inhibition of transdifferentiation. Moreover, knock‐down of Id1 in HSCs interfered with α‐SMA fiber formation, indicating a pivotal role of Id1 for fibrogenesis. Treatment of HSCs with TGF‐β1 led to increased Id1 protein expression, which was not directly mediated by the ALK5/Smad2/3, but the ALK1/Smad1 pathway. In vivo, Id1 expression and Smad1 phosphorylation were co‐induced during fibrogenesis. In conclusion, Id1 is identified as TGF‐β/ALK1/Smad1 target gene in HSCs and represents a critical mediator of transdifferentiation that might be involved in hepatic fibrogenesis. (HEPATOLOGY 2006;43:1032–1041.)
Comparative Hepatology | 2007
Lucia Wickert; Nicolas Chatain; Karin Kruschinsky; Axel M. Gressner
BackgroundIn addition to the activation of hepatic stellate cells TGF-β govern apoptosis and growth control of hepatocytes in liver injury. In non-parenchymal cells, TGF-β induces plasminogen activator inhibitor 1 (PAI-1) and connective tissue growth factor (CTGF) expression, which are involved in extra cellular matrix formation. Both genes were also regulated by glucocorticoids, which in certain cases showed antagonistic effects to the TGF-β-Smad 3 pathway. The purpose of our work was to investigate the influence of TGF-β and dexamethasone on PAI-1 and CTGF expression and secretion in primary hepatocytes.ResultsBy examining PAI-1 and CTGF mRNA and protein expression in cell lysates and cell-conditioned media under the influence of TGF-β and dexamethasone, we analysed signalling pathways controlling their expression. TGF-β and dexamethasone significantly co-induce PAI-1 and CTGF protein expression. On the other hand, we showed that TGF-β diminished a glucocorticoid receptor dependent luciferase reporter signal in Hep-G2. Inhibition of Erk downstream activation decreased TGF-β induced CTGF and PAI-1 expression to a basal level. PAI-1 was directly secreted by hepatocytes, whereas secretion of CTGF was retarded.ConclusionThe data provide evidence that beside the TGF-β-Smad 3 pathway CTGF and PAI-1 expression is additionally dependent on Erk activity in hepatocytes giving new insights into regulation of the profibrogenic proteins.
Biochemical and Biophysical Research Communications | 2002
Lucia Wickert; S. Steinkrüger; Muna Abiaka; Ursula Bolkenius; O. Purps; C. Schnabel; Axel M. Gressner
Abstract Current methods to determine the mRNA of the TGF-β-isoforms, β1, β2, and β3, are not sensitive enough to detect small alterations in the expression levels. Therefore, we established a SYBR Green I-based real-time quantitative PCR procedure with fragment-specific standards. The advantage of gene-specific quantification is the possibility to be abstain from the need to compare results with a house-keeping gene having a different sequence and PCR efficiency. Reproducibility of the results and analytical variances of the real-time PCR assays were tested. In transdifferentiating rat hepatic stellate cells (HSC) the TGF-β1-mRNA was found to be the predominant isoform expressed followed by TGF-β3 and low amounts of TGF-β2-mRNA. An alteration of the TGF-β1,-β2, and -β3 ratio during HSC transdifferentiation could not be detected. Furthermore, the GAPDH mRNA expression varied during HSC activation, and thus is not recommended as a standard in real-time PCR quantifications.
Cytokine | 2005
Katja Breitkopf; Claudia R.C. van Roeyen; Iris Sawitza; Lucia Wickert; Jürgen Floege; Axel M. Gressner
Biochemical and Biophysical Research Communications | 2004
Ursula Bolkenius; Daniela Hahn; Axel M. Gressner; Katja Breitkopf; Steven Dooley; Lucia Wickert
Matrix Biology | 2005
Susanne Lindert; Lucia Wickert; Iris Sawitza; Eliza Wiercinska; Axel M. Gressner; Steven Dooley; Katja Breitkopf
Journal of Hepatology | 2004
Lucia Wickert; Muna Abiaka; Ursula Bolkenius; Axel M. Gressner
Biologie in Unserer Zeit | 2007
Bianca Holzapfel; Lucia Wickert
World Journal of Gastroenterology | 2010
Bernd Denecke; Lucia Wickert; Yan Liu; L. Ciuclan; Steven Dooley; Nm Meindl-Beinker
GBM Fall meeting Hamburg 2007 | 2007
J. Herrmann; Lucia Wickert; Nicolas Chatain; Karin Kruschinsky; Axel M. Gressner