UCAGenomiX related publications

Du to our strong expertise in "omics" experiments and in microRNAs topics we decided to separate into 3 categories the related publications into which the Functional genomics Platform of Nice-Sophia-Antipolis is involved :
  1. Expression studies (DNA microarrays and high-throughput sequencing experiments)
  2. MicroRNA studies
  3. Miscellaneous

Defamie Virginie

 defamie@ipmc.cnrs.fr
 04 93 95 77 90
 660 route des lucioles 06560 Valbonne - Sophia-Antipolis

6 publications found

1. Gene expression profiling of human liver transplants identifies an early transcriptional signature associated with initial poor graft function.
Am J Transplant. 2008 Jun;8(6):1221-36.
Defamie V, Cursio R, Le Brigand K, Moreilhon C, Saint-Paul MC, Laurens M, Crenesse D, Cardinaud B, Auberger P, Gugenheim J, Barbry P, Mari B
CNRS, Institut de Pharmacologie Moleculaire et Cellulaire, UMR6097, 660, Route des Lucioles F-06560 Sophia Antipolis, France.

Liver ischemia-reperfusion injury occurring in orthotopic liver transplantation (OLT) may be responsible for early graft failure. Molecular mechanisms underlying initial poor graft function (IPGF) have been poorly documented in human. The purpose of this study was to identify the major transcriptional alterations occurring in human livers during OLT. Twenty-one RNA extracts derived from liver transplant biopsies taken after graft reperfusion were compared with 7 RNA derived from normal control livers. Three hundred seventy-one genes were significantly modulated and classified in molecular pathways relevant to liver metabolism, inflammatory response, cell proliferation and liver protection. Grafts were then subdivided into two groups based on their peak levels of serum aspartate amino transferase within 72 h after OLT (group 1, non-IPGF: 14 patients; group 2, IPGF: 7 patients). The two corresponding data sets were compared using a supervised prediction method. A new set of genes able to correctly classify 71% of the patients was defined. These genes were functionally associated with oxidative stress, inflammation and inhibition of cell proliferation. This study provides a comprehensive picture of the transcriptional events associated with human OLT and IPGF. We anticipate that such alterations provide a framework for the elucidation of the molecular mechanisms leading to IPGF.
Pubmed link : 18522548

2. Matrix metalloproteinase inhibition protects rat livers from prolonged cold ischemia-warm reperfusion injury.
Hepatology. 2008 Jan;47(1):177-85.
Defamie V, Laurens M, Patrono D, Devel L, Brault A, Saint-Paul MC, Yiotakis A, Barbry P, Gugenheim J, Crenesse D, Dive V, Huet, PM, Mari B
Institut de Pharmacologie Moleculaire et Cellulaire, CNRS, UMR6097, Universite de Nice-Sophia Antipolis, France.

Matrix metalloproteinases (MMPs) have been implicated in the hepatic injury induced after cold ischemia-warm reperfusion (CI-WR), by altering the extracellular matrix (ECM), but their precise role remains unknown. The hepatic MMP expression was evaluated after two conditions of CI (4oC for 24 and 42 hours: viable and nonviable livers) followed by different periods of WR, using isolated perfused rat livers. CI-WR induced moderate changes in hepatic MMP transcript levels not influenced by CI duration, while gelatinase activities accumulated in liver effluents. Therefore, the protective effect of a new phosphinic MMP inhibitor, RXP409, was tested after prolonged CI. RXP409 (10µM) was added to the UW solution and livers were preserved for 42 hours (4oC), then reperfused for 1 hour in Krebs solution (37oC), containing 20% erythrocytes. Liver viability parameters were recorded and the extent of cell necrosis was evaluated on liver biopsies, using trypan blue nuclear uptake. Treatment with RXP409 significantly improved liver function (transaminase release and bile secretion) and liver injury. In particular, the MMP inhibitor significantly modified the extent of cell death from large clusters of necrotic hepatocytes as found in control livers (2 to 60% of liver biopsies, mean: 26 ± 9%) to isolated necrotic hepatocytes as found in treated livers (0.2 to 12%, mean 3 ± 2%) (p<0.05). In conclusion, these data demonstrate that MMPs, by altering the ECM, play a major role in liver CI-WR injury leading to extensive hepatocyte necrosis and that their inhibition might prove to be a new strategy in improving preservation solutions.
Pubmed link : 18008367

3. Relationships Between Early Inflammatory Response to Bleomycin and Sensitivity to Lung Fibrosis.
Am J Respir Crit Care Med. 2007 Aug 2;
Pottier N, Chupin C, Defamie V, Cardinaud B, Sutherland R, Rios G, Gauthier F, Wolters PJ, Berthiaume Y, Barbry P, Mari B
Institut de Pharmacologie Moleculaire et Cellulaire, UMR6097, CNRS and University of Nice Sophia Antipolis, Sophia Antipolis, France.

RATIONALE. Different sensitivities to pro-fibrotic compounds such as bleomycin are observed among mouse strains. OBJECTIVES. To identify genetic factors contributing to the outcome of lung injury. METHODS. Physiological comparison of C57BL/6 sensitive and Balb/C resistant mice challenged with intra tracheal bleomycin instillation revealed several early differences: global gene expression profiles were thus established from lungs derived from the two strains, in the absence of any bleomycin administration. MEASUREMENTS AND MAIN RESULTS. Expression of 25 genes differed between the two strains. Among them, two molecules, not previously associated with pulmonary fibrosis, were identified. The first one corresponds to dipeptidyl peptidase I (DPPI), a cysteine dipeptidyl peptidase (also known as cathepsin C) essential for the activation of serine proteinases produced by immune/inflammatory cells. The second corresponds to TIMP-3, an inhibitor of matrix metalloproteases and of ADAMs such as the TNFconverting enzyme. In functional studies performed in the bleomycin induced lung fibrosis model, the level of expression of these two genes was closely correlated with specific early events associated with lung fibrosis, namely activation of PMN-derived serine proteases and TNFalpha-dependent inflammatory syndrome. Surprisingly, genetic deletion of DPPI in the context of a C57BL/6 genetic background did not protect against bleomycin-mediated fibrosis, suggesting additional function(s) for this key enzyme. CONCLUSIONS. This study highlights the importance of the early inflammatory events that follow bleomycin instillation in the development of lung fibrosis, and describes for the first time the roles that DPPI and TIMP-3 may play in this process.
Pubmed link : 17673693

4. An open-access long oligonucleotide microarray resource for analysis of the human and mouse transcriptomes.
Nucleic Acids Res. 2006 Jul 19;34(12):e87
Le Brigand K, Russell R, Moreilhon C, Rouillard JM, Jost B, Amiot F, Magnone V, Bole-Feysot C, Rostagno P, Virolle V, Defamie V, Dessen P, Williams G, Lyons P, Rios G, Mari B, Gulari E, Kastner P, Gidrol X, Freeman TC, Barbry P
CNRS, Institut de Pharmacologie Moleculaire et Cellulaire, UMR6097, 660, route des Lucioles, F-06560 Sophia Antipolis, France.

Two collections of oligonucleotides have been designed for preparing pangenomic human and mouse microarrays. A total of 148,993 and 121,703 oligonucleotides were designed against human and mouse transcripts. Quality scores were created in order to select 25,342 human and 24,109 mouse oligonucleotides. They correspond to: (i) a BLAST-specificity score; (ii) the number of expressed sequence tags matching each probe; (iii) the distance to the 3' end of the target mRNA. Scores were also used to compare in silico the two microarrays with commercial microarrays. The sets described here, called RNG/MRC collections, appear at least as specific and sensitive as those from the commercial platforms. The RNG/MRC collections have now been used by an Anglo-French consortium to distribute more than 3500 microarrays to the academic community. Ad hoc identification of tissue-specific transcripts and a approximately 80% correlation with hybridizations performed on Affymetrix GeneChiptrade mark suggest that the RNG/MRC microarrays perform well. This work provides a comprehensive open resource for investigators working on human and mouse transcriptomes, as well as a generic method to generate new microarray collections in other organisms. All information related to these probes, as well as additional information about commercial microarrays have been stored in a freely-accessible database called MEDIANTE.
Pubmed link : 17384016

5. A survey of the signaling pathways involved in megakaryocytic differentiation of the human K562 leukemia cell line by molecular and c-DNA array analysis.
Oncogene. 2006 Feb 2;25(5):781-94
Jacquel A, Herrant M, Defamie V, Belhacene N, Colosetti P, Marchetti S, Legros L, Deckert M, Mari B, Cassuto JP, Hofman P, Auberger P
INSERM U526, Physiopathologie de la Survie et de la Mort Cellulaires, Equipe Labellisee par la Ligue Nationale contre le Cancer, Universite de Nice Sophia-Antipolis, IFR50, Faculte de Medecine, Avenue de Valombrose, 06107 Nice Cedex 2, France.

The K562 cell line serves as a model to study the molecular mechanisms associated with leukemia differentiation. We show here that cotreatment of K562 cells with PMA and low doses of SB202190 (SB), an inhibitor of the p38 MAPK pathway, induced a majority of cells to differentiate towards the megakaryocytic lineage. Electronic microscopy analysis showed that K562 cells treated with PMA+SB exhibited characteristic features of physiological megakaryocytic differentiation including the presence of vacuoles and demarcation membranes. Differentiation was also accompanied by a net increase in megakaryocytic markers and a reduction of erythroid markers, especially when both effectors were present. PMA effect was selectively mediated by new PKC isoforms. Differentiation of K562 cells by the combination of PMA and SB required Erk1/2 activation, a threshold of JNK activation and p38 MAPK inhibition. Interestingly, higher concentrations of SB, which drastically activated JNK, blocked megakaryocytic differentiation, and considerably increased cell death in the presence of PMA. c-DNA microarray membranes and PCR analysis allow us to identify a set of genes modulated during PMA-induced K562 cell differentiation. Several gene families identified in our screening, including ephrins receptors and some angiogenic factors, had never been reported so far to be regulated during megakaryocytic differentiation.
Pubmed link : 16186797

6. Tumor cell-mediated induction of the stromal factor stromelysin-3 requires heterotypic cell contact-dependent activation of specific protein kinase C isoforms.
J Biol Chem. 2005 Jan 14;280(2):1272-83. Epub 2004 Oct 27.
Louis K, Guerineau N, Fromigue O, Defamie V, Collazos A, Anglard P, Shipp MA, Auberger P, Joubert D, Mari B
INSERM U526, IFR50, Faculte de Medecine Pasteur, 06107 Nice, France.

Stromelysin-3 (ST3, MMP-11) has been shown to be strongly overexpressed in stromal fibroblasts of most invasive human carcinomas. However, the molecular mechanisms leading to ST3 expression in nonmalignant fibroblasts remain unknown. The aim of the present study was to analyze the signaling pathways activated in normal pulmonary fibroblasts after their interaction with non-small cell lung cancer (NSCLC) cells and leading to ST3 expression. The use of selective signaling pathway inhibitors showed that conventional and novel protein kinase Cs (PKC) were required for ST3 induction, whereas Src kinases exerted a negative control. We observed by both conventional and real time confocal microscopy that green fluorescent protein-tagged PKCalpha and PKCepsilon, but not PKCdelta, transfected in fibroblasts, accumulate selectively at the cell-cell contacts between fibroblasts and tumor cells. In agreement, RNAi-mediated depletion of PKCalpha and PKCepsilon, but not PKCdelta significantly decreased co-culture-dependent ST3 production. Finally, a tetracycline-inducible expression model allowed us to confirm the central role of these PKC isoforms and the negative regulatory function of c-Src in the control of ST3 expression. Altogether, our data emphasize signaling changes occurring in the tumor microenvironment that may define new stromal targets for therapeutic intervention.
Pubmed link : 15509588