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16 results on '"Sekkali, Belaid"'

4. [beta]-Catenin downregulation attenuates ischemic cardiac remodeling through enhanced resident precursor cell differentiation

Author

Zelarayan, Laura C., Noack, Claudia, Sekkali, Belaid, Kmecova, Jana, Gehrke, Christina, Renger, Anke, Zafiriou, Maria-Patapia, van der Nagel, Roel, Dietz, Rainer, de Windt, Leon J., Balligand, Jean-Luc, and Bergmann, Martin W.

Subjects
Cell differentiation -- Research, Heart cells -- Properties, Cell proliferation -- Research, Cellular control mechanisms -- Research, Science and technology
Abstract

We analyzed the effect of conditional, [alpha]MHC-dependent genetic [beta]-catenin depletion and stabilization on cardiac remodeling following experimental infarct. [beta]-Catenin depletion significantly improved 4-week survival and left ventricular (LV) function (fractional shortening: [CT.sup.[delta]ex3-6]: 24 [+ or -] 1.9%; [beta]-[cat.sup.[delta]ex3-6]; 30.2 [+ or -] 1.6%, P < 0.001). [beta]-Catenin stabilization had opposite effects. No significant changes in adult cardiomyocyte survival or hypertrophy were observed in either transgenic line. Associated with the functional improvement, LV scar cellularity was altered: [beta]-catenin-depleted mice showed a marked subendocardial and subepicardial layer of small [cTnT.sup.pos] cardiomyocytes associated with increased expression of cardiac lineage markers Tbx5 and GATA4. Using a Cre-dependent lacZ reporter gene, we identified a noncardiomyocyte cell population affected by [alpha]MHC-driven gene recombination localized to these tissue compartments at baseline. These cells were found to be cardiac progenitor cells since they coexpressed markers of proliferation (Ki67) and the cardiomyocyte lineage ([alpha]MHC, GATA4, Tbx5) but not cardiac Troponin T (cTnT). The cell population overlaps in part with both the previously described c-[kit.sup.pos] and stem cell antigen-1 [(Sca-1).sup.pos] precursor cell population but not with the Islet-[1.sup.pos] precursor cell pool. An in vitro coculture assay of highly enriched (>95%) Sca-[1.sup.pos] cardiac precursor cells from [beta]-catenin-depleted mice compared to cells isolated from control littermate demonstrated increased differentiation toward [alpha]-[actin.sup.pos] and [cTnT.sup.pos] cardiomyocytes after 10 days ([CT.sup.[delta]ex3-6]: 38.0 [+ or -] 1.0% [alpha]-[actin.sup.pos] [beta]-[cat.sup.[delta]ex3-6]: 49.9 [+ or -] 2.4% [alpha]-[actin.sup.pos], P < 0.001). We conclude that [beta]-catenin depletion attenuates postinfarct LV remodeling in part through increased differentiation of [GATA4.sup.pos]/Sca-[1.sup.pos] resident cardiac progenitor cells.

Published
2008

5. Dnmt3a-mediated inhibition of Wnt in cardiac progenitor cells improves differentiation and remote remodeling after infarction.

Author

UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, UCL - (SLuc) Département de médecine interne et services associés, UCL - (SLuc) Service de cardiologie pédiatrique, De Pauw, Aurelia, Andre, Emilie, Sekkali, Belaid, Bouzin, Caroline, Esfahani, Hrag, Barbier, Nicolas, Loriot, Axelle, De Smet, Charles, Vanhoutte, Laetitia, Moniotte, Stéphane, Gerber, Bernhard, di Mauro, Vittoria, Catalucci, Daniele, Feron, Olivier, Hilfiker-Kleiner, Denise, Balligand, Jean-Luc, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, UCL - (SLuc) Département de médecine interne et services associés, UCL - (SLuc) Service de cardiologie pédiatrique, De Pauw, Aurelia, Andre, Emilie, Sekkali, Belaid, Bouzin, Caroline, Esfahani, Hrag, Barbier, Nicolas, Loriot, Axelle, De Smet, Charles, Vanhoutte, Laetitia, Moniotte, Stéphane, Gerber, Bernhard, di Mauro, Vittoria, Catalucci, Daniele, Feron, Olivier, Hilfiker-Kleiner, Denise, and Balligand, Jean-Luc

Abstract

Adult cardiac progenitor cells (CPCs) display a low capacity to differentiate into cardiomyocytes in injured hearts, strongly limiting the regenerative capacity of the mammalian myocardium. To identify new mechanisms regulating CPC differentiation, we used primary and clonally expanded Sca-1+ CPCs from murine adult hearts in homotypic culture or coculture with cardiomyocytes. Expression kinetics analysis during homotypic culture differentiation showed downregulation of Wnt target genes concomitant with increased expression of the Wnt antagonist, Wnt inhibitory factor 1 (Wif1), which is necessary to stimulate CPC differentiation. We show that the expression of the Wif1 gene is repressed by DNA methylation and regulated by the de novo DNA methyltransferase Dnmt3a. In addition, miR-29a is upregulated early during CPC differentiation and downregulates Dnmt3a expression, thereby decreasing Wif1 gene methylation and increasing the efficiency of differentiation of Sca-1+ CPCs in vitro. Extending these findings in vivo, transient silencing of Dnmt3a in CPCs subsequently injected in the border zone of infarcted mouse hearts improved CPC differentiation in situ and remote cardiac remodeling. In conclusion, miR-29a and Dnmt3a epigenetically regulate CPC differentiation through Wnt inhibition. Remote effects on cardiac remodeling support paracrine signaling beyond the local injection site, with potential therapeutic interest for cardiac repair.

Published
2017

6. Dnmt3a-mediated inhibition of Wnt in cardiac progenitor cells improves differentiation and remote remodeling after infarction

Author

De Pauw, Aurelia, primary, Andre, Emilie, additional, Sekkali, Belaid, additional, Bouzin, Caroline, additional, Esfahani, Hrag, additional, Barbier, Nicolas, additional, Loriot, Axelle, additional, De Smet, Charles, additional, Vanhoutte, Laetitia, additional, Moniotte, Stéphane, additional, Gerber, Bernhard, additional, di Mauro, Vittoria, additional, Catalucci, Daniele, additional, Feron, Olivier, additional, Hilfiker-Kleiner, Denise, additional, and Balligand, Jean-Luc, additional

Published
2017
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7. Paracrine nitric oxide induces expression of cardiac sarcomeric proteins in adult progenitor cells through soluble guanylyl cyclase/cyclic-guanosine monophosphate and Wnt/β-catenin inhibition

Author

De Pauw, Aurelia, primary, Massion, Paul, additional, Sekkali, Belaid, additional, Andre, Emilie, additional, Dubroca, Caroline, additional, Kmecova, Jana, additional, Bouzin, Caroline, additional, Friart, Ann, additional, Sibille, Catherine, additional, Gilon, Patrick, additional, De Mulder, Delphine, additional, Esfahani, Hrag, additional, Strapart, Adrien, additional, Martherus, Ruben, additional, Payen, Valéry, additional, Sonveaux, Pierre, additional, Brouckaert, Peter, additional, Janssens, Stefan, additional, and Balligand, Jean-Luc, additional

Published
2016
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8. Caveolin-1 downregulation prevents eNOS uncoupling by angiotensin II through inhibition of NADPH oxidase assembly and activation in caveolae of endothelial cells

Author

UCL - Cliniques universitaires Saint-Luc, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - SSS/LDRI - Louvain Drug Research Institute, UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, UCL - (SLuc) Service de médecine interne générale, Lobysheva, Irina, Balligand, Jean-Luc, Rath, Géraldine, Sekkali, Belaid, Feron, Olivier, Dessy, Chantal, Gallez, Bernard, 6th Int Conf on Biol, Chemistry, and Therapeutic Applications of Nitric Oxide/2nd Int Conf NO and Cancer/10th Annual Meeting of the Nitric-Oxide-Soc-Japan, UCL - Cliniques universitaires Saint-Luc, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - SSS/LDRI - Louvain Drug Research Institute, UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, UCL - (SLuc) Service de médecine interne générale, Lobysheva, Irina, Balligand, Jean-Luc, Rath, Géraldine, Sekkali, Belaid, Feron, Olivier, Dessy, Chantal, Gallez, Bernard, and 6th Int Conf on Biol, Chemistry, and Therapeutic Applications of Nitric Oxide/2nd Int Conf NO and Cancer/10th Annual Meeting of the Nitric-Oxide-Soc-Japan

Published
2010

9. Caveolin-1 Downregulation Reduces NADPH Oxidaso Assembly and Reverses eNOS Uncoupling

Author

UCL - Cliniques universitaires Saint-Luc, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - SSS/LDRI - Louvain Drug Research Institute, UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, UCL - (SLuc) Service de médecine interne générale, Lobysheva, Irina, Balligand, Jean-Luc, Rath, Géraldine, Sekkali, Belaid, Feron, Olivier, Dessy, Chantal, Gallez, Bernard, 82nd Scientific Session of the American-Heart-Association, UCL - Cliniques universitaires Saint-Luc, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - SSS/LDRI - Louvain Drug Research Institute, UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, UCL - (SLuc) Service de médecine interne générale, Lobysheva, Irina, Balligand, Jean-Luc, Rath, Géraldine, Sekkali, Belaid, Feron, Olivier, Dessy, Chantal, Gallez, Bernard, and 82nd Scientific Session of the American-Heart-Association

Published
2009

10. Rosuvastatin restores NO-dependent endothelial function by increasing vascular PPARg and SOD1 expression

Author

UCL - Cliniques universitaires Saint-Luc, UCL - MD/MINT - Département de médecine interne, Desjardins, Fanny, Balligand, Jean-Luc, Sekkali, Belaid, Verreth, Wim, Smith, Graham, Holvoet, Paul, 80th Annual Scientific Session of the American-Heart-Association, UCL - Cliniques universitaires Saint-Luc, UCL - MD/MINT - Département de médecine interne, Desjardins, Fanny, Balligand, Jean-Luc, Sekkali, Belaid, Verreth, Wim, Smith, Graham, Holvoet, Paul, and 80th Annual Scientific Session of the American-Heart-Association

Published
2007

11. Cardiomyocyte-specific overexpression of beta3-adrenoceptors attenuates the hypertrophic response to catecholamines in vivo

Author

UCL - Cliniques universitaires Saint-Luc, UCL - MD/MINT - Département de médecine interne, Beige, Catharina, Vanoverschelde, Jean-Louis, Balligand, Jean-Luc, Sekkali, Belaid, Tavernier, Genevieve, Pouleur, Anne-Catherine, Bertrand, Luc, Hilfiker-Kleiner, Denise, Langin, Dominique, 80th Annual Scientific Session of the American-Heart-Association, UCL - Cliniques universitaires Saint-Luc, UCL - MD/MINT - Département de médecine interne, Beige, Catharina, Vanoverschelde, Jean-Louis, Balligand, Jean-Luc, Sekkali, Belaid, Tavernier, Genevieve, Pouleur, Anne-Catherine, Bertrand, Luc, Hilfiker-Kleiner, Denise, Langin, Dominique, and 80th Annual Scientific Session of the American-Heart-Association

Published
2007

12. Erythropoietin Preserves the Endothelial Differentiation Capacity of Cardiac Progenitor Cells and Reduces Heart Failure during Anticancer Therapies

Author

Hoch, Melanie, primary, Fischer, Philipp, additional, Stapel, Britta, additional, Missol-Kolka, Ewa, additional, Sekkali, Belaid, additional, Scherr, Michaela, additional, Favret, Fabrice, additional, Braun, Thomas, additional, Eder, Matthias, additional, Schuster-Gossler, Karin, additional, Gossler, Achim, additional, Hilfiker, Andres, additional, Balligand, Jean-Luc, additional, Drexler, Helmut, additional, and Hilfiker-Kleiner, Denise, additional

Published
2011
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16. Human HMG box transcription factor HBP1: a role in hCD2 LCR function.

Author

Zhuma, Talgat, Tyrrell, Richard, Sekkali, Belaid, Skavdis, George, Saveliev, Alexander, Tolaini, Mauro, Roderick, Kathleen, Sedgwick, Trisha, Smerdon, Steve, Sedgwick, Steve, Festenstein, Richard, and Kioussis, Dimitris

Subjects
GENES, GENETICS, HYDROXYMETHYLGLUTARYL coenzyme A reductases, CHROMATIN, DNA-protein interactions
Abstract

The locus control region (LCR) of the human CD2 gene (hCD2) confers T cell-specific, copy-dependent and position-independent gene expression in transgenic mice. This LCR consists of a strong T cell-specific enhancer and an element without enhancer activity (designated HSS3), which is required for prevention of position effect variegation (PEV) in transgenic mice. Here, we identified the HMG box containing protein-1 (HBP1) as a factor binding to HSS3 of the hCD2 LCR. Within the LCR, HBP1 binds to a novel TTCATT-CATTCA sequence that is higher in affinity than other recently reported HBP1-binding sites. Mice transgenic for a hCD2 LCR construct carrying a deletion of the HBP1-binding sequences show a propensity for PEV if the transgene integrates in a heterochromatic region of the chromosome such as the centromere or telomere. We propose that HBP1 plays an important role in chromatin opening and remodelling activities by binding to and bending the DNA, thus allowing DNA-protein and/or protein-protein interactions, which increase the probability of establishing an active locus. [ABSTRACT FROM AUTHOR]

Published
1999
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