Régis BLAISE | UPMC Sorbonne Universités (original) (raw)

Papers by Régis BLAISE

J'ai croisé énormément de personnes depuis mes premiers pas dans un laboratoire de recherche en 1... more J'ai croisé énormément de personnes depuis mes premiers pas dans un laboratoire de recherche en 1995. Il m'est impossible de toutes les citer, mais elles m'ont accompagné pendant ces 24 années et certaines d'entre elles ont été une véritable source d'inspiration et d'admiration. Tout d'abord un grand merci aux membres du jury, qui m'ont fait l'honneur et/ou l'amitié d'accepter de participer à cette HDR, pendant la période de l'année la plus chargée qui soit. Tout d'abord Marie-Luce Bochaton-Pialat, Jean-Luc Olivier et Grégoire Vandecasteele pour leur bienveillance en tant que rapporteur de cette HDR, ainsi que Anne Nègre-Salvayre, Jean-Noël Octave, et Xavier Houard. Je souhaite ensuite remercier tout particulièrement Isabelle Limon de me faire confiance depuis presque 10 ans, avec bienveillance mais exigence. Isabelle est grandement responsable du scientifique et de l'enseignant que je suis aujourd'hui, sans son soutien, sa combativité, ses conseils, son objectivité et son amitié, je ne serai pas là où j'en suis. Merci à toi pour tout. Un immense merci à Pierre Vincent, pour tout ce que j'ai appris avec lui. Merci pour ton sens critique, ta rigueur et ton intégrité scientifique, des valeurs essentielles à mes yeux. Merci également à son équipe pour les moments passés et surtout à venir. Un merci spécial aux étudiants que j'ai encadrés et qui ont eu souvent à supporter mon caractère pas toujours facile. Votre motivation et votre investissement dans ces projets ont été décisifs, vous les avez fait grandir et mûrir, vous avez eu le même effet sur moi et j'espère que j'en ai fait autant pour vous. Un merci tout particulier à Benjamin Vallin, Justine Hur et Yohan Legueux-Cajgfinger pour tout. Merci à tous les membres de l'équipe CMLV, présents ou passés, qui ont participé à tous les niveaux à ces deux projets :

Journal of Cell Science, 2020

Arterial remodeling in hypertension and intimal hyperplasia involves inflammation and disrupted f... more Arterial remodeling in hypertension and intimal hyperplasia involves inflammation and disrupted flow, both of which contribute to smooth muscle cell dedifferentiation and proliferation. In this context, our previous results identified phosphoinositide 3-kinase gamma (PI3Kγ) as an essential factor in inflammatory processes of the arterial wall. Here, we identified for the first time a kinase-independent role of nonhematopoietic PI3Kγ in the vascular wall during intimal hyperplasia using PI3Kγ deleted mice and mice expressing a kinase-dead version of the enzyme. Moreover, we found that the absence of PI3Kγ in VSMCs leads to the modulation of cell proliferation associated with an increase in intracellular cAMP levels. Real-time analysis of cAMP dynamics revealed that PI3Kγ modulates the degradation of cAMP in primary vascular smooth muscle cells (VSMC) independent of its kinase activity through the regulation of the phosphodiesterase (PDE) 4 enzyme. Importantly, the use of an N-termina...

Archives of Cardiovascular Diseases Supplements, 2019

The FASEB Journal, 2018

Cerebral amyloid angiopathy (CAA) is a major contributor to Alzheimer's disease (AD) pathogenesis... more Cerebral amyloid angiopathy (CAA) is a major contributor to Alzheimer's disease (AD) pathogenesis. Like AD, CAA is often accompanied by marked inflammation, aggravating associated vasculopathies. No evidence-based prevention or treatment strategies are available. Here, we evaluate the possible beneficial effect of a diet enriched with docosahexaenoic acid (DHA), which is known to attenuate inflammation in CAA. Tg2576 mice, a transgenic model of AD/CAA, were fed a DHA-enriched diet starting at 2 mo of age and ending at 10, 14, or 18 mo of age. b-Amyloid (Ab)-peptide deposition and bleeding were visualized by immunohistochemistry or histochemistry on coronal sections of the brain. DHA, arachidonic acid, and eicosanoid levels were measured by liquid chromatography/mass spectrometry or GC-MS. DHA-enriched diet throughout aging limits the accumulation of vascular Ab peptide deposits as well as the likelihood of microhemorrhages. There is a strong correlation between systemic 12hydroxyeicosatetraenoic acid (HETE) levels and the size of the area affected by both vascular amyloid deposits and hemorrhages. The lowest levels of 12-HETE, a lipid-derived proinflammatory product of 12-lipoxygenase (LOX), were found in DHA-fed mice. In vitro experiments performed on amyloid vascular smooth muscle cells showed that a 12-LOX inhibitor almost completely blocked the Ab 1-40 peptide-induced apoptosis of these cells. This study yet again highlights the important role of inflammation in CAA pathogenesis and identifies potential new targets for preventive care.

Biochimica et biophysica acta, 2018

Here, we cloned a new family of four adenylyl cyclase (AC) splice variants from interleukin-1β (I... more Here, we cloned a new family of four adenylyl cyclase (AC) splice variants from interleukin-1β (IL-1β)-transdifferentiated vascular smooth muscle cells (VSMCs) encoding short forms of AC8 that we have named "AC8E-H". Using biosensor imaging and biochemical approaches, we showed that AC8E-H isoforms have no cyclase activity and act as dominant-negative regulators by forming heterodimers with other full-length ACs, impeding the traffic of functional units towards the plasma membrane. The existence of these dominant-negative isoforms may account for an unsuspected additional degree of cAMP signaling regulation. It also reconciles the induction of an AC in transdifferentiated VSMCs with the vasoprotective influence of cAMP. The generation of alternative splice variants of ACs may constitute a generalized strategy of adaptation to the cell's environment whose scope had so far been ignored in physiological and/or pathological contexts.

Atherosclerosis, 2017

Antihypertensive effect of refined olive oil enriched with hydroxytyrosol in a mice model of type... more Antihypertensive effect of refined olive oil enriched with hydroxytyrosol in a mice model of type 2 diabetes mellitus: implication of smooth muscle cells relaxation

Journal of Visualized Experiments, 2016

Biologie Aujourd'hui, 2016

-En réponseà différents types de stress vasculaires, les cellules musculaires lisses de la paroi ... more -En réponseà différents types de stress vasculaires, les cellules musculaires lisses de la paroi vasculaire (CMLV) changent de phénotype et acquièrent la capacité de répondreà des signaux anormaux. Ce phénomène les prédisposeà participer au développement de pathologies vasculaires majeures telles que l'athérosclérose et certaines complications post-angioplastie comme la resténose. La voie de l'adénosine monophosphate cyclique (AMPc) joue un rôle central dans l'intégration des stimuli environnants et dans l'élaboration des réponses cellulaires. La spécificité des signaux transmis est assurée par la compartimentation subcellulaire spatiale et temporelle de l'AMPc. Cette compartimentation tientà la diversité (i) des protéines régulant directement ou indirectement la synthèse, la dégradation, ou l'extrusion de l'AMPc ; (ii) des effecteurs intracellulaires de l'AMPc ; (iii) des isoformes de toutes ces protéines aux propriétés biochimiques et aux mécanismes de régulations uniques ; (iv) de protéines d'échafaudage les rassemblant en complexes macromoléculaires. Cette revue illustre en quoi le changement du profil d'expression des adénylyl cyclases (AC) peut jouer un rôle critique dans l'intégration des signaux et la réponse des cellules musculaires et etre associéà un remodelage vasculaire pathologique. Elle illustreégalement pourquoi il est pertinent de considérer,à nouveau, les AC comme des cibles thérapeutiques d'intérêt.

Cardiovascular Research, 2014

Biochemical Journal, 1997

Hormone-sensitive lipase (HSL) catalyses the rate-limiting step of adipose tissue lipolysis. The ... more Hormone-sensitive lipase (HSL) catalyses the rate-limiting step of adipose tissue lipolysis. The human HSL gene is composed of nine exons encoding the adipocyte form and a testis-specific coding exon. Northern blot analyses showed that human adipocytes express a 2.8 kb HSL mRNA, suggesting the presence of a short (20-150 bp) 5ʹ untranslated region (5ʹ-UTR). A single 5ʹ-UTR of approx. 70 nt was detected in RNase H mapping experiments. Two 5ʹ-UTRs of 70 and 170 nt respectively were obtained by rapid amplification of cDNA ends and cDNA library screenings. RNase protection experiments, with probes derived from the two products, showed that human adipocyte HSL mRNA contains only the 70 nt product. Primer extension analysis mapped the transcriptional start site 74 nt upstream of the start codon. In HT29, a human cell line expressing HSL, the presence of the short or the long 5ʹ-UTR is mutually exclusive. The short and long 5ʹ-UTR exons were located 1.5 and approx. 13 kb respectively upstr...

Osteoarthritis and Cartilage, 2007

Purpose: MR T 1ρ mapping has been proposed as a promising diagnostic tool for the early detection... more Purpose: MR T 1ρ mapping has been proposed as a promising diagnostic tool for the early detection of cartilage degeneration in osteoarthritis (OA). Because there are investigations towards establishing a relationship between T 1ρ values and matrix biochemistry in cartilage, it becomes increasingly important to elucidate the effect of orientation relative to the static magnetic field, B 0 , an impeding factor between a direct correlation of T 1ρ relaxation times and biochemical composition of cartilage, and thus a potential source of spurious conclusions. The purpose of this study is to obtain quantitative information regarding the effect of B 0 orientation on T 1ρ profiles in intact and OA cartilage as well as to explore the use of different spin-locking frequencies to minimize the orientation effect. Methods: Five cartilage specimens were imaged on a 3.0 T GE MR scanner using a quadrature wrist coil: three from OA patients who underwent total knee replacement and two from cadaver knees with no history of diagnosed OA. The 3D T 1ρ-weighted images were obtained using a previously developed sequence, with time of spin-lock = 0, 10, 40, 80 ms, slice thickness = 2 mm, in-plane resolution = 0.3 x 0.3 mm, spin-lock frequencies at 500 Hz and 1 kHz respectively. Data were acquired at 3 different orientations with respect to the B 0-0°, 90°, and 55°, the "magic angle" (angles were assessed relative to the radial zone). MR visible marks were used to ensure the same slices were scanned among these three orientations. Two to three matching slices from each specimen were semi-automatically segmented and the mean T 1ρ values as well as T 1ρ line profiles were obtained. A paired t-test was used to compare T 1ρ average between the 3 different orientations as well as to compare the differences between different spin-locking frequencies. Results: T 1ρ values were elevated at 55°significantly relative to 0°and 90°at both spin locking frequencies (P < 0.05, Table 1 and Figure 1). T 1ρ relaxation times at 1 kHz are significantly higher than those at 500 Hz (P < 0.05). Observing the average difference regarding the horizontal orientation as a reference we see a 12.1% difference when comparing 0°and 90°, and a 11.2% difference when comparing 0°and 55°at a spin-lock frequency of 500 Hz. At 1 kHz, the % difference is decreased to 9.0% and 7.3%, respectively.

The Journal of pharmacology and experimental therapeutics, 1997

It is now clearly established that alpha-2 adrenergic receptors can be subdivided in three pharma... more It is now clearly established that alpha-2 adrenergic receptors can be subdivided in three pharmacological subtypes (alpha-2A, alpha-2B and alpha-2C) encoded by distinct genes (alpha 2C10, alpha 2C2 and alpha 2C4, respectively, in humans). Whereas the study of the regulation of the human alpha-2A adrenergic receptor and of the promoter region of the alpha 2C10 gene has being greatly helped by the availability of the colon carcinoma cell line HT29, the study of the other human receptor subtypes has thus far been limited to homologous desensitization/down-regulation in transfected cells, because of the lack of human cellular models constitutively-expressing alpha-2B or alpha-2C adrenergic receptors. Several human cell lines were thus screened, in an attempt to find such models. Radioligand binding studies with [3H]RX821002 and [3H]MK912, reverse transcription-polymerase chain reactions and RNase mapping experiments with pairs of primers and riboprobes specific for each subtype demonst...

Osteoarthritis and Cartilage, 2008

In contrast, cytomegalovirus promoter-driven Sp1 overexpression further enhanced Il-1-induced ADA... more In contrast, cytomegalovirus promoter-driven Sp1 overexpression further enhanced Il-1-induced ADAMTS-4 expression. Expression of constitutive ADAMTS-5 was not affected by any of the agents. Conclusions: These results provide pharmacological and genetic evidence for the importance of Sp1 in ADAMTS-4 gene regulation by Il-1.

Mechanisms of Development, 2005

Mice deficient for the homeobox gene Six1 display defects in limb muscles consistent with the Six... more Mice deficient for the homeobox gene Six1 display defects in limb muscles consistent with the Six1 expression in myogenic cells. In addition to its myogenic expression domain, Six1 has been described as being located in digit tendons and as being associated with connective tissue patterning in mouse limbs. With the aim of determining a possible involvement of Six1 in tendon development, we have carefully characterised the non-myogenic expression domain of the Six1 gene in mouse and chick limbs. In contrast to previous reports, we found that this non-myogenic domain is distinct from tendon primordia and from tendons defined by scleraxis expression. The non-myogenic domain of Six1 expression establishes normally in the absence of muscle, in Pax3 K/K mutant limbs. Moreover, the expression of scleraxis is not affected in early Six1 K/K mutant limbs. We conclude that the expression of the Six1 gene is not related to tendons and that Six1, at least on its own, is not involved in limb tendon formation in vertebrates. Finally, we found that the posterior domain of Six1 in connective tissue is adjacent to that of the secreted factor Sonic hedgehog and that Sonic hedgehog is necessary and sufficient for Six1 expression in posterior limb regions.

Journal of Cell Science, 2007

Atherogenesis begins with the transfer of monocytes from the lumen to the intimal layer of arteri... more Atherogenesis begins with the transfer of monocytes from the lumen to the intimal layer of arteries. The paracrine activity acquired by these monocytes shifts vascular smooth muscle cells from a contractile-quiescent to a secretory-proliferative phenotype, allowing them to survive and migrate in the intima. Transformed and relocated, they also start to produce and/or secrete inflammatory enzymes, converting them into inflammatory cells. Activation of the Notch pathway, a crucial determinant of cell fate, regulates some of the new features acquired by these cells as it triggers vascular smooth muscle cells to grow and inhibits their death and migration. Here, we evaluate whether and how the Notch pathway regulates the cell transition towards an inflammatory or de-differentiated state. Activation of the Notch pathway by the notch ligand Delta1, as well as overexpression of the active form of Notch3, prevents this phenomenon [initiated by interleukin 1β (IL-1β)], whereas inhibiting the...

Journal of Biological Chemistry, 2000

A testicular form of hormone-sensitive lipase (HSL tes), a triacylglycerol lipase, and cholestero... more A testicular form of hormone-sensitive lipase (HSL tes), a triacylglycerol lipase, and cholesterol esterase, is expressed in male germ cells. Northern blot analysis showed HSL tes mRNA expression in early spermatids. Immunolocalization of the protein in human and rodent seminiferous tubules indicated that the highest level of expression occurred in elongated spermatids. We have previously shown that 0.5 kilobase pairs of the human HSL tes promoter directs testis-specific expression of a chloramphenicol acetyltransferase reporter gene in transgenic mice and determined regions binding nuclear proteins expressed in testis but not in liver (Blaise,

Journal of Biological Chemistry, 1999

The testicular isoform of hormone-sensitive lipase (HSL tes) is encoded by a testis-specific exon... more The testicular isoform of hormone-sensitive lipase (HSL tes) is encoded by a testis-specific exon and 9 exons common to the testis and adipocyte isoforms. In mouse, HSL tes mRNA appeared during spermiogenesis in round spermatids. Two constructs containing 1.4 and 0.5 kilobase pairs (kb) of the human HSL tes gene 5-flanking region cloned upstream of the chloramphenicol acetyltransferase gene were microinjected into mouse oocytes. Analyses of enzyme activity in male and female transgenic mice showed that 0.5 kb of the HSL tes promoter was sufficient to direct expression only in testis. Cell transfection experiments showed that CREM, a testis-specific transcriptional activator, does not transactivate the HSL tes promoter. Using gel retardation assays, four testis-specific binding regions (TSBR) were identified using testis and liver nuclear extracts. The testis-specific protein binding on TSBR4 was selectively competed by a probe containing a SRY/Sox protein DNA recognition site. Sox5 and Sox6 which are expressed in post-meiotic germ cells bound TSBR4. Mutation of the AACAAAG motif in TSBR4 abolished the binding. Moreover, binding of the high mobility group domain of Sox5 induced a bend within TSBR4. Together, our results showed that 0.5 kb of the human HSL tes promoter bind Sox proteins and contain cis-acting elements essential for the testis specificity of HSL.

Journal of Biological Chemistry, 2013

Authors are urged to introduce these corrections into any reprints they distribute. Secondary (ab... more Authors are urged to introduce these corrections into any reprints they distribute. Secondary (abstract) services are urged to carry notice of these corrections as prominently as they carried the original abstracts.