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Transforming growth factor-β and fibrosis

World Journal of Gastroenterology 2007年第22期13卷 3056-3062页

作者： Franck Verrecchia alain mauviel INSERM U697 Paris 75010 France

Transforming growth factor-β （TGF-β）, a prototype of multifunctional cytokine, is a key regulator of extracellular matrix （ECM） assembly and remodeling. Specifically, TGF-β isoforms have the ability to induce the expression of ECM proteins in mesenchymal cells, and to stimulate the production of protease inhibitors that prevent enzymatic breakdown of the ECM. Elevated TGF-β expression in affected organs, and subsequent deregulation of TGF-β functions, correlates with the abnormal connective tissue deposition observed during the onset of fibrotic diseases. During the last few years, tremendous progress has been made in the understanding of the molecular aspects of intracellular signaling downstream of the TGF-β receptors. In particular, Smad proteins, TGF-β receptor kinase substrates that translocate into the cell nucleus to act as transcription factors, have been studied extensively. The role of Smad3 in the transcriptional regulation of type I collagen gene expression and in the development of fibrosis, demonstrated both/n vitro and in animal models with a targeted deletion of Smad3, is of critical importance because it may lead to novel therapeutic strategies against these diseases. This review focuses on the mechanisms underlying Smad modulation of fibrillar collagen expression and how it relates to fibrotic processes.

关键词： Collagen Connective tissue growth factor Fibrosis Smad Transforming growth factor-β

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c-Fos overexpression increases the proliferation of human hepatocytes by stabilizing nuclear Cyclin D1

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World Journal of Gastroenterology 2008年第41期14卷 6339-6346页

作者： Meryem Güller Kahina Toualbi-Abed Agnès Legrand Laurence Michel alain mauviel Dominique Bernuau Fanny Daniel Institut National de laSanté et de la Recherche Médicale U697 Hpital Saint-Louis Institut National de la Santé et de la RechercheMédicale U591 Faculté de Médecine Necker Institut National de la Santé et de la RechercheMédicale U773 Centre de Recherche Bichat Beaujon CRB3and Université Paris 7 Denis Diderot site Bichat

AIM： To investigate the effect of stable c-Fos over- expression on immortalized human hepatocyte （IHH） proliferation. METHODS： IHHs stably transfected with c-Fos （IHH- Fos） or an empty vector （IHH-C） were grown in me- dium supplemented with 1% serum or stimulated with 10% serum. Cell proliferation was assessed by cell counts, 3H-thymidine uptake and flow cytometry analyses. The levels of cell cycle regulatory proteins （Cyclin DI, E, A） cyclin dependent kinases （cdk） cdk2, cdk4, cdk6, and their inhibitors p15, p16, p21, p27, total and phosphorylated GSK-3β and epidermal growth factor receptor （EGF-R） were assayed by Western blotting. Analysis of O/c/in D1 mRNA levels was performed by reverse transcription-polymerase chain reaction and real-time polymerase chain reaction （PCR） analysis. Stability of Cyclin DI was studied by cycloheximide blockade experiments. RESULTS： Stable c-Fos overexpression increased cell proliferation under low serum conditions and resulted in a two-fold increase in [3H]-thymidine incorpora- tion following serum addition. Cell cycle analysis by flow cytometry showed that c-Fos accelerated the cell cycle kinetics. Following serum stimulation, Cyclin D1 was more abundantly expressed in c-Fos overexpress- ing cells. Cyclin D1 accumulation did not result from increased transcriptional activation, but from nuclear stabilization. Overexpression of c-Fos correlated with higher nuclear levels of inactive phosphorylated GSK- 3β, a kinase involved in Cyclin D1 degradation and higher levels of EGF-R mRNA, and EGF-R protein com- pared to IHH-C both in serum starved, and in serum stimulated cells. Abrogation of EGF-R signalling in IHH- Fos by treatment with AG1478, a specific EGF-R tyro- sine kinase inhibitor, prevented the phosphorylation of GSK-3β induced by serum stimulation and decreased Cyclin D1 stability in the nucleus. CONCLUSION： Our results clearly indicate a positive role for c-Fos in cell cycle regulation in hepatocytes. Importantly, we delineate

关键词： c-Fos Cyclin DI GSK-3 Cell growth, Cell cycle Hepatoma Epidermal growth factor

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Fe-doped olivine and char for in-bed elimination of gasification tars in an air-blown fluidised bed reactor coupled with oxidative hot gas filtration

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Carbon Resources Conversion 2022年第4期5卷 271-288页

作者： Miguel Ruiz Adam Schnitzer Claire Courson Guillain mauviel LRGP CNRSUniversity of LorraineENSIC1 Rue GrandvilleNancyFrance University of Lorraine LERMaBENSTIB27 Rue Philippe S´eguinPO Box 1041F-88051 EpinalFrance Institut of Chemistry and Processes for Energy Environment and HealthICPEES–UMR 7515University of Strasbourg25 Rue Becquerel67087 StrasbourgFrance

Gasification experiments were carried out in a pilot scale fluid bed reactor operated under allothermal mode and low fluidisation regime with iron-doped olivine and char as catalyst for in-situ tar *** catalyst combination resulted in a reduction of 50%in the overall tar yield with respect to the reference ***,the integration of an oxidative Hot Gas Filtration unit downstream the gasification reactor led to a further reduction in overall tar yield and relatively clean gas was obtained(approx.1 g/Nm3,benzene-free).The tar dew point of the resulting producer gas was estimated to 80℃,only 40℃ above the threshold value recommended for its valorisation in standard internal combustion ***,catalyst elutriation and char hold-up took place to a large extent inside the *** analysis of catalyst samples at different Time-On-Stream(TOS)revealed:(i)a considerable loss of iron oxides during the first hour of test because of the interparticle mechanical attrition(mostly surface abrasion)and partial reduction of hematite to magnetite and wustite but,stable composition at higher TOS,(ii)the loss of the iron oxide coverage of Fe/olivine particles and the formation of agglomerates with increasing TOS and,(iii)the amount of carbon deposited in the surface of the Fe/olivine particles increased with TOS,but in any case,these carbon deposits can be completely oxidized above 650℃.

关键词： Gasification Tar Oxidative hot gas filtration Char Iron-doped olivine

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