Publications by authors named "Eric Mathieu"

17 Publications

  • Page 1 of 1

The true colours of the Formidable Pygmy Grasshopper ( Günther, 1974) from the Sava region (Madagascar).

Zookeys 2021 7;1042:41-50. Epub 2021 Jun 7.

University of Zagreb, Faculty of Science, Department of Biology, Division of Zoology, Evolution Lab, Rooseveltov trg 6, HR-10000 Zagreb, Croatia University of Zagreb Zagreb Croatia.

The Formidable Pygmy Grasshopper, Günther, 1974 (Tetrigidae: 'Malagasy Metrodorinae'), is certainly a stunning, extraordinary insect. Despite the fact that the species was described almost 50 years ago, its beauty had remained completely hidden until recently. The bright yellow colouration of the minute warts on its dorsal hump and even brighter purple-yellowish colouration of its abdomen have been, tragically, completely lost in museum specimens. Luckily, photographs of three live females taken in 2007, 2009 and 2015 were recently uploaded to the iNaturalist platform by the first author of this paper, where they were identified as by the middle and last authors. Along with a male and a female discovered in the MNHN collections (Paris) and the holotype female, these are the only records of the species. All six records are presented and depicted in the present study, and the variation of the species is discussed for the first time. This rare species seems to be endemic to NE Madagascar, a region of truly wonderful diversity.
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http://dx.doi.org/10.3897/zookeys.1042.66381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203595PMC
June 2021

Insensitivity of dental pulp stem cells migration to substrate stiffness.

Biomaterials 2021 Aug 15;275:120969. Epub 2021 Jun 15.

Inserm UMR-S1121, Centre de Recherche en Biomédecine de Strasbourg (CRBS), 1 rue Eugène Boeckel, 67084, Strasbourg, France; Université de Strasbourg, Faculté de Chirurgie Dentaire, 8 rue Sainte Elisabeth, 67000, Strasbourg, France; Fédération de Médecine Translationnelle, Strasbourg, France. Electronic address:

Dental pulp stem cells (DPSCs) are a promising cell source for regeneration of dental pulp. Migration is a key event but influence of the microenvironment rigidity (5 kPa at the center of dental pulp to 20 GPa for the dentin) is largely unknown. Mechanical signals are transmitted from the extracellular matrix to the cytoskeleton, to the nuclei, and to the chromatin, potentially regulating gene expression. To identify the microenvironmental influence on migration, we analyzed motility on PDMS substrates with stiffness increasing from 1.5 kPa up to 2.5 MPa. We found that migration speed slightly increases as substrate stiffness decreases in correlation with decreasing focal adhesion size. Motility is relatively insensitive to substrate stiffness, even on a bi-rigidity PDMS substrate where DPSCs migrate without preferential direction. Migration is independent of both myosin II activity and YAP translocation after myosin II inhibition. Additionally, inhibition of Arp2/3 complex leads to significant speed decrease for all rigidities, suggesting contribution of the lamellipodia in the migration. Interestingly, the chromatin architecture remains stable after a 7-days exposure on the PDMS substrates for all rigidity. To design scaffold mimicking dental pulp environment, similar DPSCs migration for all rigidity, leaves field open to choose this mechanical parameter.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120969DOI Listing
August 2021

Deficiency of the SMOC2 matricellular protein impairs bone healing and produces age-dependent bone loss.

Sci Rep 2020 09 9;10(1):14817. Epub 2020 Sep 9.

Developmental Biology and Stem Cells Department, Institute of Genetics and of Molecular and Cellular Biology (IGBMC), 1 rue Laurent Fries, BP 10142, 67404, Illkirch, France.

Secreted extracellular matrix components which regulate craniofacial development could be reactivated and play roles in adult wound healing. We report a patient with a loss-of-function of the secreted matricellular protein SMOC2 (SPARC related modular calcium binding 2) presenting severe oligodontia, microdontia, tooth root deficiencies, alveolar bone hypoplasia, and a range of skeletal malformations. Turning to a mouse model, Smoc2-GFP reporter expression indicates SMOC2 dynamically marks a range of dental and bone progenitors. While germline Smoc2 homozygous mutants are viable, tooth number anomalies, reduced tooth size, altered enamel prism patterning, and spontaneous age-induced periodontal bone and root loss are observed in this mouse model. Whole-genome RNA-sequencing analysis of embryonic day (E) 14.5 cap stage molars revealed reductions in early expressed enamel matrix components (Odontogenic ameloblast-associated protein) and dentin dysplasia targets (Dentin matrix acidic phosphoprotein 1). We tested if like other matricellular proteins SMOC2 was required for regenerative repair. We found that the Smoc2-GFP reporter was reactivated in adjacent periodontal tissues 4 days after tooth avulsion injury. Following maxillary tooth injury, Smoc2 mutants had increased osteoclast activity and bone resorption surrounding the extracted molar. Interestingly, a 10-day treatment with the cyclooxygenase 2 (COX2) inhibitor ibuprofen (30 mg/kg body weight) blocked tooth injury-induced bone loss in Smoc2 mutants, reducing matrix metalloprotease (Mmp)9. Collectively, our results indicate that endogenous SMOC2 blocks injury-induced jaw bone osteonecrosis and offsets age-induced periodontal decay.
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http://dx.doi.org/10.1038/s41598-020-71749-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481257PMC
September 2020

Mechanobiologically induced bone-like nodules: Matrix characterization from micro to nanoscale.

Nanomedicine 2020 10 29;29:102256. Epub 2020 Jun 29.

Université de Reims Champagne Ardenne, BIOS EA 4691, Reims, France; Université de Reims Champagne Ardenne, UFR d'Odontologie, Reims, France. Electronic address:

In bone tissue engineering, stem cells are known to form inhomogeneous bone-like nodules on a micrometric scale. Herein, micro- and nano-infrared (IR) micro-spectroscopies were used to decipher the chemical composition of the bone-like nodule. Histological and immunohistochemical analyses revealed a cohesive tissue with bone-markers positive cells surrounded by dense mineralized type-I collagen. Micro-IR gathered complementary information indicating a non-mature collagen at the top and periphery and a mature collagen within the nodule. Atomic force microscopy combined to IR (AFM-IR) analyses showed distinct spectra of "cell" and "collagen" rich areas. In contrast to the "cell" area, spectra of "collagen" area revealed the presence of carbohydrate moieties of collagen and/or the presence of glycoproteins. However, it was not possible to determine the collagen maturity, due to strong bands overlapping and/or possible protein orientation effects. Such findings could help developing protocols to allow a reliable characterization of in vitro generated complex bone tissues.
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http://dx.doi.org/10.1016/j.nano.2020.102256DOI Listing
October 2020

Chromatin de-condensation by switching substrate elasticity.

Sci Rep 2018 08 23;8(1):12655. Epub 2018 Aug 23.

Inserm UMR-S1121, 11 rue Humann, 67085, Strasbourg, France.

Mechanical properties of the cellular environment are known to influence cell fate. Chromatin de-condensation appears as an early event in cell reprogramming. Whereas the ratio of euchromatin versus heterochromatin can be increased chemically, we report herein for the first time that the ratio can also be increased by purely changing the mechanical properties of the microenvironment by successive 24 h-contact of the cells on a soft substrate alternated with relocation and growth for 7 days on a hard substrate. An initial contact with soft substrate caused massive SW480 cancer cell death by necrosis, whereas approximately 7% of the cells did survived exhibiting a high level of condensed chromatin (21% heterochromatin). However, four consecutive hard/soft cycles elicited a strong chromatin de-condensation (6% heterochromatin) correlating with an increase of cellular survival (approximately 90%). Furthermore, cell survival appeared to be reversible, indicative of an adaptive process rather than an irreversible gene mutation(s). This adaptation process is associated with modifications in gene expression patterns. A completely new approach for chromatin de-condensation, based only on mechanical properties of the microenvironment, without any drug mediation is presented.
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http://dx.doi.org/10.1038/s41598-018-31023-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6107547PMC
August 2018

Retinoic Acid Excess Impairs Amelogenesis Inducing Enamel Defects.

Front Physiol 2016 6;7:673. Epub 2017 Jan 6.

Developmental Biology and Stem Cells Department, Institute of Genetics and Molecular and Cellular Biology (IGBMC)Illkirch, France; Centre National de la Recherche Scientifique, UMR 7104Illkirch, France; Institut National de la Santé et de la Recherche Médicale, U 964Illkirch, France; Université de StrasbourgIllkirch, France; Faculté de Chirurgie Dentaire, Université de StrasbourgStrasbourg, France.

Abnormalities of enamel matrix proteins deposition, mineralization, or degradation during tooth development are responsible for a spectrum of either genetic diseases termed or acquired enamel defects. To assess if environmental/nutritional factors can exacerbate enamel defects, we investigated the role of the active form of vitamin A, retinoic acid (RA). Robust expression of RA-degrading enzymes and in developing murine teeth suggested RA excess would reduce tooth hard tissue mineralization, adversely affecting enamel. We employed a protocol where RA was supplied to pregnant mice as a food supplement, at a concentration estimated to result in moderate elevations in serum RA levels. This supplementation led to severe enamel defects in adult mice born from pregnant dams, with most severe alterations observed for treatments from embryonic day (E)12.5 to E16.5. We identified the enamel matrix proteins (), (), and () as target genes affected by excess RA, exhibiting mRNA reductions of over 20-fold in lower incisors at E16.5. RA treatments also affected bone formation, reducing mineralization. Accordingly, craniofacial ossification was drastically reduced after 2 days of treatment (E14.5). Massive RNA-sequencing (RNA-seq) was performed on E14.5 and E16.5 lower incisors. Reductions in (a key transcriptional regulator of bone and enamel differentiation) and its targets were observed at E14.5 in RA-exposed embryos. RNA-seq analysis further indicated that bone growth factors, extracellular matrix, and calcium homeostasis were perturbed. Genes mutated in human AI () were reduced in expression at E16.5. Our observations support a model in which elevated RA signaling at fetal stages affects dental cell lineages. Thereafter enamel protein production is impaired, leading to permanent enamel alterations.
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http://dx.doi.org/10.3389/fphys.2016.00673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217128PMC
January 2017

Enamel and dental anomalies in latent-transforming growth factor beta-binding protein 3 mutant mice.

Eur J Oral Sci 2017 02;125(1):8-17

Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.

Latent-transforming growth factor beta-binding protein 3 (LTBP-3) is important for craniofacial morphogenesis and hard tissue mineralization, as it is essential for activation of transforming growth factor-β (TGF-β). To investigate the role of LTBP-3 in tooth formation we performed micro-computed tomography (micro-CT), histology, and scanning electron microscopy analyses of adult Ltbp3-/- mice. The Ltbp3-/- mutants presented with unique craniofacial malformations and reductions in enamel formation that began at the matrix formation stage. Organization of maturation-stage ameloblasts was severely disrupted. The lateral side of the incisor was affected most. Reduced enamel mineralization, modification of the enamel prism pattern, and enamel nodules were observed throughout the incisors, as revealed by scanning electron microscopy. Molar roots had internal irregular bulbous-like formations. The cementum thickness was reduced, and microscopic dentinal tubules showed minor nanostructural changes. Thus, LTBP-3 is required for ameloblast differentiation and for the formation of decussating enamel prisms, to prevent enamel nodule formation, and for proper root morphogenesis. Also, and consistent with the role of TGF-β signaling during mineralization, almost all craniofacial bone components were affected in Ltbp3-/- mice, especially those involving the upper jaw and snout. This mouse model demonstrates phenotypic overlap with Verloes Bourguignon syndrome, also caused by mutation of LTBP3, which is hallmarked by craniofacial anomalies and amelogenesis imperfecta phenotypes.
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http://dx.doi.org/10.1111/eos.12328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5260799PMC
February 2017

New insight in the biological integration of polytetrafluoroethylene from an explant used for diaphragm repair.

J Biomater Appl 2017 Jan 11;31(6):844-850. Epub 2016 Nov 11.

1 Institut National de la Santé et de la Recherche Médicale, UMR_S 1121, Strasbourg, France.

Congenital diaphragmatic hernia is a severe disease requiring diaphragm replacement mostly with expanded polytetrafluoroethylene. Unfortunately, the recurrence rate is high due to prosthesis failure with significant morbidity for the child. To provide a better understanding of the integration and possible failure processes of the biomaterial implanted in humans, we conducted electron microscopical and mechanical assessments on a prosthesis explant from a child with congenital diaphragmatic hernia presenting a recurrence. Our findings show a major penetration of connective tissue into the expanded polytetrafluoroethylene on the rough side, whereas the smooth side presents few tissue colonization. This penetration is more important in the central area (area A) with large collagen bundles and layers, in comparison to the peripheral areas without prosthesis failure (area B), where few extracellular matrix is produced. The connective tissue penetrates the prosthesis in depth. In contrast, the peripheral areas with prosthesis failure (area C) show very few cells and extracellular matrix, with an oriented organization in comparison to areas A and B. Obviously, the forces applied on the implanted material modulate the cellular behavior of the newly developed tissues. Atomic force microscopic measurements of the biomaterials' surfaces may explain some cellular behaviors according to areas with or without failure.
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http://dx.doi.org/10.1177/0885328216676757DOI Listing
January 2017

Kinetics of deposition and stability of pyrocatechol -FeIII coordinated films.

Mater Sci Eng C Mater Biol Appl 2017 Mar 2;72:620-624. Epub 2016 Dec 2.

Unité Mixte de Recherche 1121, Institut National de la Santé et de la Recherche Médicale, 11 rue Humann, 67085 Strasbourg Cedex, France; Université de Strasbourg, Faculté de Chirurgie Dentaire, 8 rue Sainte Elisabeth, 67000 Strasbourg, France. Electronic address:

Metal coordination between polyphenols and metal cations like Fe allows to produce conformal homogeneous and robust coatings on a vast variety of materials. The deposition kinetics and the stability of the obtained films are however only poorly investigated. In the present article it is shown that rough, granular but pinhole free coatings up to 50nm in thickness can be obtained in a one pot manner using pyrocatechol (Pyr)/Fe mixtures at different stoichiometries (with Fe/Pyr ratios equal to 0.55 or 1.10) provided the deposition time is extended up to 24h. More importantly, we show that these films are dissolved upon oxidation of Pyr in cyclic voltammetry experiments. When the films deposited during short durations are rinsed with buffer and subsequently re-exposed to Pyr containing solution, they undergo partial dissolution most probably through a ligand exchange process. Such a dissolution process does not occur anymore in the same conditions, when the deposition time is increased above 5h. All Pyr-Fe based films can be stabilized by a post-deposition of a polyelectrolyte multilayer film based on the alternated adsorption of poly(allylamine hydrochloride) and the sodium salt of poly(styrene sulfonate). The deposition of 5 bilayers of these polyelectrolytes allows suppressing the dissolution of Pyr-Fe based films produced for short deposition times.
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http://dx.doi.org/10.1016/j.msec.2016.11.123DOI Listing
March 2017

Mutations in the latent TGF-beta binding protein 3 (LTBP3) gene cause brachyolmia with amelogenesis imperfecta.

Hum Mol Genet 2015 Jun 10;24(11):3038-49. Epub 2015 Feb 10.

Department of Medical Genetics, University of Antwerp and Antwerp University Hospital, Prins Boudewijnlaan 43, Edegem 2650, Belgium.

Inherited dental malformations constitute a clinically and genetically heterogeneous group of disorders. Here, we report on four families, three of them consanguineous, with an identical phenotype, characterized by significant short stature with brachyolmia and hypoplastic amelogenesis imperfecta (AI) with almost absent enamel. This phenotype was first described in 1996 by Verloes et al. as an autosomal recessive form of brachyolmia associated with AI. Whole-exome sequencing resulted in the identification of recessive hypomorphic mutations including deletion, nonsense and splice mutations, in the LTBP3 gene, which is involved in the TGF-beta signaling pathway. We further investigated gene expression during mouse development and tooth formation. Differentiated ameloblasts synthesizing enamel matrix proteins and odontoblasts expressed the gene. Study of an available knockout mouse model showed that the mutant mice displayed very thin to absent enamel in both incisors and molars, hereby recapitulating the AI phenotype in the human disorder.
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http://dx.doi.org/10.1093/hmg/ddv053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4424950PMC
June 2015

Cell guidance into quiescent state through chromatin remodeling induced by elastic modulus of substrate.

Biomaterials 2015 Jan 29;37:144-55. Epub 2014 Oct 29.

INSERM UMR 1121, 11 rue Humann, 67085 Strasbourg, France; Faculté de Chirurgie Dentaire, Université de Strasbourg, 8 rue Sainte-Elisabeth, 67000 Strasbourg, France; Fédération de Médecine Translationnelle, Strasbourg, France. Electronic address:

Substrate stiffness is known to strongly influence the fate of adhering cells. Yet, little is known about the influence of the substrate stiffness on chromatin. Chromatin integrates a multitude of biochemical signals interpreted by activation or gene silencing. Here we investigate for the first time the organization of chromatin of epithelial cells on substrate with various mechanical properties. On stiff substrates (100-200 kPa), where cells preferentially adhere, chromatin is mainly found in its euchromatin form. Decreasing the Young modulus to 50 kPa is correlated with a partial shift from euchromatin to heterochromatin. On very soft substrates (≪10 kPa) this is accompanied by cell lysis. On these very soft substrates, histone deacetylase inhibition by adding a drug preserves acetylated histone and thus maintains the euchromatin form, thereby keeping intact the nuclear envelope as well as a residual intermediate filament network around the nucleus. This allows cells to survive in a non-adherent state without undergoing proliferation. When transfer on a stiff substrate these cells retain their capacity to adhere, to spread and to enter a novel mitotic cycle. A similar effect is observed on soft substrates (50 kPa) without need of histone deacetylase inhibition. These new results suggest that on soft substrates cells might enter in a quiescence state. Cell quiescence may thus be triggered by the Young modulus of a substrate, a major result for strategies focusing on the design of scaffold in tissue engineering.
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http://dx.doi.org/10.1016/j.biomaterials.2014.10.023DOI Listing
January 2015

Nanoscale precipitation coating: the deposition of inorganic films through step-by-step spray-assembly.

ACS Nano 2010 Aug;4(8):4792-8

Centre National de la Recherche Scientifique, Institut Charles Sadron, UPR 22, 23 rue Loess, 67083 Strasbourg, France.

Thin films and surface coatings play an important role in basic and applied research. Here we report on a new, versatile, and simple method ("precipitation coating") for the preparation of inorganic films, based on the alternate spraying of complementary inorganic salt solutions against a receiving surface on which the inorganic deposit forms. The method applies whenever the solubility of the deposited material is smaller than that of the salts in the solutions of the reactants. The film thickness is controlled from nanometers to hundreds of micrometers simply by varying the number of spraying steps; 200 spray cycles, corresponding to less than 15 min deposition time, yield films with thicknesses exceeding one micrometer and reaching tens of micrometers in some cases. The new solution-based process is also compatible with conventional layer-by-layer assembly and permits the fabrication of multimaterial sandwich-like coatings.
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http://dx.doi.org/10.1021/nn1005667DOI Listing
August 2010

The retinoblastoma gene and its product are targeted by ICBP90: a key mechanism in the G1/S transition during the cell cycle.

Oncogene 2005 Nov;24(49):7337-45

Inserm UMR S392, Faculté de Pharmacie, 74 route du Rhin, BP 60024, 67401 Illkirch Cedex, France.

The retinoblastoma protein (pRB) is encoded by the RB1 gene whose promoter contains several putative binding sites for ICBP90 (Inverted CCAAT box Binding Protein of 90 kDa), a transcriptional regulator of the topoisomerase IIalpha gene. ICBP90 has two consensus binding sites for pRB in its primary sequence. Here, we show that pRB and ICBP90 co-immunoprecipitate in cell extracts of proliferating human lung fibroblasts and of proliferating or confluent Jurkat cells. GST pull-down assays and immunocytochemistry, after cell synchronization in late G1 phase, confirmed this interaction. Overexpression of ICBP90 induces downregulation of pRB expression in lung fibroblasts as a result of mRNA decrease. DNA chromatin immunoprecipitation experiment shows that ICBP90 binds to the RB1 gene promoter under its methylated status. Overexpression of ICBP90 increases the S and G2/M phase cell fractions of serum-starved lung fibroblasts as assessed by flow cytometry analysis and increases topoisomerase IIalpha expression. Together, these results show that ICBP90 regulates pRB at the protein and gene transcription levels, thus favoring the entry into the S phase of the cells. We propose that ICBP90 overexpression, found in cancer cells, is involved in the altered checkpoint controls occurring in cancerogenesis.
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http://dx.doi.org/10.1038/sj.onc.1208878DOI Listing
November 2005

TCR pathway involves ICBP90 gene down-regulation via E2F binding sites.

Biochem Pharmacol 2005 Aug;70(4):570-9

INSERM UMR-S 392, and Laboratoire de Physiopathologie Cellulaire & Moléculaire et Infection, Institut de Parasitolgie et de Pathologie Tropicale, Faculté de Médecine, 3 rue Koeberlé, 67000 Strasbourg, France.

Antigen-induced cell death is essential for function, growth and differentiation of T-lymphocytes through legation of the T cell receptor. Since TCR-induced cell death occurs at late G1 checkpoint of the cell cycle and considering that ICBP90 is critical for G1/S transition, we studied the ICBP90 regulation through the TCR pathway in Jurkat cells. ICBP90 expression was strongly decreased after TCR triggering concomitantly to cyclin D3 and topoisomerase IIalpha expression decreases. Cell stimulation with PMA and/or calcium ionophore A23187 down-regulated ICBP90 expression. The decrease of ICBP90 protein and mRNA expressions was accompanied with cell growth arrest. A luciferase reporter assay demonstrated that activation of TCR pathways inhibit ICBP90 gene promoter activity. Three consensus E2F binding sites (called from E2F-a to E2F-c) were identified in the ICBP90 gene promoter and were subjected to mutations. The E2F-a, located in a highly active promoter fragment, shows a strong positive functional activity in proliferating cells. E2F-a and E2F-c binding sites are involved in the TCR-induced down-regulation of ICBP90 gene transcription. Altogether, our data demonstrate that TCR signaling pathways regulate ICBP90 gene expression through pRb/E2F complex. We propose that ICBP90 down-regulation is a key event in G1 arrest preceding T cell death.
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http://dx.doi.org/10.1016/j.bcp.2005.05.012DOI Listing
August 2005

Phosphorylation of ICBP90 by protein kinase A enhances topoisomerase IIalpha expression.

Biochem Biophys Res Commun 2004 Jun;319(2):590-5

Institut National de la Santé et de la Recherche Médicale, Inserm UMR-S 392, Faculté de Pharmacie, 74 route du Rhin, B.P. 60024, 67401 Illkirch Cedex, France.

Inverted CCAAT box binding protein of 90kDa (ICBP90) is a nuclear protein involved in the topoisomerase IIalpha (TopoIIalpha) gene expression. It belongs to a family of E3 ligases of the RING finger type and its expression is deregulated in cancer cells. Previous studies have shown that high expression of ICBP90 may impair the control of G1/S transition of the cell cycle in various cancer cell lines. Since PKA signaling pathway is involved in G1/S transition of the cell cycle, the aim of the present study was to investigate whether cAMP signaling pathways involve phosphorylation of ICBP90. Here, we show that phosphorylation of ICBP90 through the cAMP signaling pathway accelerates exit of forskolin-treated cells from the G1 phase and increases binding of ICBP90 to the ICB2 element of the TopoIIalpha gene promoter with a subsequent increase of TopoIIalpha expression. We identify S298 of ICBP90 as target for PKA. We propose that cAMP signaling pathway enhances TopoIIalpha expression through ICBP90 phosphorylation, which may be one of the major events involved in the G1/S transition.
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http://dx.doi.org/10.1016/j.bbrc.2004.05.028DOI Listing
June 2004

Intraluminal pressure increases vascular neuronal nitric oxide synthase expression.

J Hypertens 2003 May;21(5):937-42

Institut National de la Santé et de la Recherche Médicale (INSERM) Unit 541, Hôpital lariboisiére, Cedex 10, France.

Background: Development of high blood pressure (BP) is associated with an increased expression of neuronal nitric oxide synthase (nNOS) in vascular smooth muscle cells.

Methods: We investigated whether or not changes in intraluminal pressure affect nNOS expression in carotid arteries of normotensive rats. Expression of nNOS and other NOS isoforms was determined by Western blot analysis in rat carotid arteries maintained up to 24 h at different levels of intraluminal pressure in an organ culture system.

Results: Expression of nNOS in arteries exposed to 80 mmHg was stable for the duration of the experiment. Increasing intraluminal pressure to 200 mmHg transiently augmented nNOS expression at 9 h, both in intact arteries and in arteries where the endothelium and the adventitia were removed. The expression of endothelial NOS (eNOS) was also augmented under similar experimental conditions, but only after 24 h exposure. The ERK1/2 kinase cascade inhibitor PD 98059 significantly impaired the expression of nNOS in arteries exposed to 200 mmHg for 9 h. However, the angiotensin AT(1) antagonist candesartan and the angiotensin converting enzyme inhibitor perindoprilat did not have any effect under the same experimental conditions. Finally, the preferential nNOS inhibitor S-methyl-L-thiocitrulline significantly augmented the contraction evoked by angiotensin II in arteries exposed to 200 mmHg, but not in those maintained at 80 mmHg intraluminal pressure for 9 h.

Conclusion: These results show that transmural pressure increases nNOS expression and NO release in rat smooth muscle cells by a mechanism involving the mitogen-activated protein kinase pathway, but independent from the local formation of angiotensin II.
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http://dx.doi.org/10.1097/00004872-200305000-00018DOI Listing
May 2003

Inhibition by glucocorticoids of the interleukin-1beta-enhanced expression of the mast cell growth factor SCF.

Br J Pharmacol 2002 Apr;135(7):1634-40

INSERM U425, Université Louis Pasteur Strasbourg I, 67401 Illkirch cedex, France.

1. Stem cell factor (SCF) is a major mast cell growth factor that promotes differentiation and chemotaxis of mast cells and inhibits their apoptosis. 2. We evaluated the effect of interleukin (IL)-1beta, a major pro-inflammatory cytokine, on the constitutive expression of SCF and studied the effects of two glucocorticoids, budesonide and dexamethasone, on the IL-1beta-enhanced SCF expression. 3. Human lung fibroblasts in culture were serum-starved for 48 h and treated with IL-1beta, budesonide and/or RU486. SCF cDNA was quantified after total RNA reverse transcription by on-line fluorescent polymerase chain reaction. SCF protein was quantified by ELISA. 4. IL-1beta induced an increase in SCF mRNA (+91% at 2.5 h) and protein production (+32%) by human lung fibroblasts in culture (P<0.001). 5. Budesonide inhibited IL-1beta-induced SCF mRNA expression (-68%) at 2.5 h and even more so at 10 h (-192%) (P<0.001). The expression of SCF protein also decreased by 3.5-fold at 10 h. Results were similar with dexamethasone. The glucocorticoid antagonist RU486 cancelled the effects induced by the glucocorticoids. 6. Increased SCF mRNA levels were associated with increased stability of this mRNA as measured after treatment with actinomycin D (1.9-fold at 2.5 h). Budesonide decreased this IL-1beta-enhanced stability by about 1.5-fold (P<0.001). 7. We conclude that in 'inflammatory' conditions, mimicked in vitro by IL-1beta, glucocorticoid treatment inhibits expression of the mast cell growth factor SCF. The reduced number and activation of mast cells observed in the bronchi of asthmatic patients treated by glucocorticoids may be due in part to this effect.
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http://dx.doi.org/10.1038/sj.bjp.0704617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1573283PMC
April 2002
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