Jean Ripoche

University of Bordeaux, Burdeos, Aquitaine, France

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Publications (89)288.55 Total impact

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    ABSTRACT: Prompt recognition of severe renal impairment could improve the early management of critically ill patients. We compared the value of kinetic eGFR, plasma neutrophil gelatinase-associated lipocalin (NGAL), and urine tissue inhibitor of metalloproteinase-2 and urine insulin-like growth factor-binding protein 7 ([TIMP-2]*[IGFBP7]) in predicting short-term recovery from AKI and major adverse kidney events. During the 6-month study period, 245 patients were admitted to our intensive care unit. This study included 57 consecutive patients presenting with AKI within the first 24 hours after admission. AKI markers were evaluated at inclusion (day 0) and 24 hours later (day 1). Kinetic eGFR was calculated on day 1 according to serum creatinine evolution. Renal recovery was defined as normalization of serum creatinine with reversal of oliguria within 48 hours. Major adverse kidney events included death, need for RRT, or persistence of renal dysfunction at hospital discharge. Plasma NGAL and [TIMP-2]*[IGFBP7] predicted renal recovery, with area under the receiver-operating characteristic curve (AUC-ROC) values between 0.70 and 0.79 at inclusion. Although plasma NGAL values frequently reached the maximal measurement range, their decrease on day 1 predicted recovery. The kinetic eGFR calculation after initial resuscitation provided the best AUC-ROC value for renal recovery, at 0.87. The best predictions for major adverse kidney events were provided by [TIMP-2]*[IGFBP7] and kinetic eGFR (equal AUC-ROCs of 0.81). Combining AKI markers in addition to clinical prediction models improved the discrimination and reclassification of patients who will recover from AKI or suffer from major adverse kidney events. Biomarkers of kidney damage predicted short-term renal recovery and major adverse kidney events for an unselected cohort of critically ill patients. Calculating the kinetic eGFR imposed a delay after initial resuscitation but provided a good diagnostic and prognostic approach. The utility of functional and damage AKI marker combinations in addition to clinical information requires validation in larger prospective studies. Copyright © 2015 by the American Society of Nephrology.
    No preview · Article · Sep 2015 · Clinical Journal of the American Society of Nephrology
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    ABSTRACT: The role of platelets extends beyond hemostasis. The pivotal role of platelets in inflammation has shed new light on the natural history of conditions associated with acute or chronic inflammation. Beyond the preservation of vascular integrity, platelets are essential to tissue homeostasis and platelet-derived products are already used in the clinics. Unanticipated was the role of platelets in the adaptative immune response, allowing a renewed conceptual approach of auto-immune diseases. Platelets are also important players in cancer growth and dissemination. Platelets fulfill most of their functions through the expression of still incompletely characterized membrane-bound or soluble mediators. Among them, CD154 holds a peculiar position, as platelets represent a major source of CD154 and as CD154 contributes to most of these new platelet attributes. Here, we provide an overview of some of the new frontiers that the study of platelet CD154 is opening, in inflammation, tissue homeostasis, immune response, hematopoiesis and cancer.
    Full-text · Article · Mar 2015
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    ABSTRACT: Shear stress is one of mechanical constraints which are exerted by blood flow on endothelial cells (ECs). To adapt to shear stress, ECs align in the direction of flow through adherens junction (AJ) remodeling. However, mechanisms regulating ECs alignment under shear stress are poorly understood. The scaffold protein IQ domain GTPase activating protein 1 (IQGAP1) is a scaffold protein which couples cell signaling to the actin and microtubule cytoskeletons and is involved in cell migration and adhesion. IQGAP1 also plays a role in AJ organization in epithelial cells. In this study, we investigated the potential IQGAP1 involvement in the endothelial cells alignment under shear stress. Progenitor-derived endothelial cells (PDECs), transfected (or not) with IQGAP1 small interfering RNA, were exposed to a laminar shear stress (1.2 N/m(2)) and AJ proteins (VE-cadherin and β-catenin) and IQGAP1 were labeled by immunofluorescence. We show that IQGAP1 is essential for ECs alignment under shear stress. We studied the role of IQGAP1 in AJs remodeling of PDECs exposed to shear stress by studying cell localization and IQGAP1 interactions with VE-cadherin and β-catenin by immunofluorescence and Proximity Ligation Assays. In static conditions, IQGAP1 interacts with VE-cadherin but not with β-catenin at the cell membrane. Under shear stress, IQGAP1 lost its interaction from VE-cadherin to β-catenin. This "switch" was concomitant with the loss of β-catenin/VE-cadherin interaction at the cell membrane. This work shows that IQGAP1 is essential to ECs alignment under shear stress and that AJ remodeling represents one of the mechanisms involved. These results provide a new approach to understand ECs alignment under to shear stress.
    Preview · Article · Nov 2013 · PLoS ONE

  • No preview · Article · Mar 2013 · Journal des Maladies Vasculaires
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    ABSTRACT: Introduction Renal resistive index (RI), determined by Doppler ultrasonography, directly reveals and quantifies modifications in renal vascular resistance. The aim of this study was to evaluate if mean arterial pressure (MAP) is determinant of renal RI in septic, critically ill patients suffering or not from acute kidney injury (AKI). Methods This prospective observational study included 96 patients. AKI was defined according to RIFLE criteria and transient or persistent AKI according to renal recovery within 3 days. Results Median renal RIs were 0.72 (0.68-0.75) in patients without AKI and 0.76 (0.72-0.80) in patients with AKI (P=0.001). RIs were 0.75 (0.72-0.79) in transient AKI and 0.77 (0.70-0.80) in persistent AKI (P=0.84). RI did not differ in patients given norepinephrine infusion and was not correlated with norepinephrine dose. RI was correlated with MAP (ρ= -0.47; P=0.002), PaO2/FiO2 ratio (ρ= -0.33; P=0.04) and age (ρ=0.35; P=0.015) only in patients without AKI. Conclusions A poor correlation between renal RI and MAP, age, or PaO2/FiO2 ratio was found in septic and critically ill patients without AKI compared to patients with AKI. These findings suggest that determinants of RI are multiple. Renal circulatory response to sepsis estimated by Doppler ultrasonography cannot reliably be predicted simply from changes in systemic hemodynamics. As many factors influence its value, the interest in a single RI measurement at ICU admission to determine optimal MAP remains uncertain.
    Full-text · Article · Sep 2012 · Critical care (London, England)

  • No preview · Article · Sep 2012 · Néphrologie & Thérapeutique

  • No preview · Article · Sep 2012 · Néphrologie & Thérapeutique
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    Dataset: Figure S1
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    ABSTRACT: Morphology of human cultured podocytes and expression of nephrin, a podocyte specific marker. (A) The morphology of human cultured podocytes was observed by light microscopy: undifferentiated cells (left panel-33°C) and differentiated cells (right panel-37°C). (B) Immunofluorescence of nephrin in human cultured podocytes showed a diffuse cytoplasmic expression in undifferentiated cells (left panel-33°C) and a focal membrane expression associated with a cytoplasmic labelling in differentiated cells (right panel-37°C). (TIF)
    Preview · Dataset · May 2012
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    ABSTRACT: IQGAP1 is a scaffold protein that interacts with proteins of the cytoskeleton and the intercellular adhesion complex. In podocytes, IQGAP1 is associated with nephrin in the glomerular slit diaphragm (SD) complex, but its role remains ill-defined. In this work, we investigated the interaction of IQGAP1 with the cytoskeleton and SD proteins in podocytes in culture, and its role in podocyte migration and permeability. Expression, localization, and interactions between IQGAP1 and SD or cytoskeletal proteins were determined in cultured human podocytes by Western blot (WB), immunocytolocalization (IC), immunoprecipitation (IP), and In situ Proximity Ligation assay (IsPL). Involvement of IQGAP1 in migration and permeability was also assessed. IQGAP1 expression in normal kidney biopsies was studied by immunohistochemistry. IQGAP1 expression by podocytes increased during their in vitro differentiation. IC, IP, and IsPL experiments showed colocalizations and/or interactions between IQGAP1 and SD proteins (nephrin, MAGI-1, CD2AP, NCK 1/2, podocin), podocalyxin, and cytoskeletal proteins (α-actinin-4). IQGAP1 silencing decreased podocyte migration and increased the permeability of a podocyte layer. Immunohistochemistry on normal human kidney confirmed IQGAP1 expression in podocytes and distal tubular epithelial cells and also showed an expression in glomerular parietal epithelial cells. In summary, our results suggest that IQGAP1, through its interaction with components of SD and cytoskeletal proteins, is involved in podocyte barrier properties.
    Full-text · Article · May 2012 · PLoS ONE
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    Dataset: Figure S2
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    ABSTRACT: Western blot analysis of IQGAP1, nephrin, MAGI-1, CD2AP, podocin, NCK 1/2, α-actinin-4, β-catenin, podocalyxin and β-actin expression in cultured podocyte extracts. Western blot analyses were performed on all these proteins during podocyte differentiation. Protein extracts were from undifferentiated (permissive temperature of 33°C, Day 0 (D0)) and differentiated (non-permissive temperature of 37°C, Day 16 (D16)) cultured immortalized podocytes, and a second human kidney lysate (HKL); MW: Molecular weight (kDa). (TIF)
    Preview · Dataset · May 2012
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    Dataset: Figure S3
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    ABSTRACT: FAK expression in podocytes. Immunofluorescence of FAK showed a similar expression in control podocytes (A) and in siRNA IQGAP1 transfected podocytes (B). Characteristics of FAK antibody: rabbit antibody, dilution 1/100, Upstate Biotechnology, Massachusetts, USA. (TIF)
    Preview · Dataset · May 2012
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    Dataset: Figure S5
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    ABSTRACT: IQGAP1 glomerular expression and localization in normal kidney tissue. All sections from normal kidneys (6) are figured. In normal glomeruli, IQGAP1 labelling (green) was continuous, corresponding to podocytes. IQGAP1 was also expressed in parietal epithelial, endothelial and distal tubular cells. Nuclear staining with DAPI is also represented. Immunohistochemistry experiments were performed on paraffin sections from normal kidneys (6). Analysis was performed with confocal microscopy. Microscope sections, 0.5 µm. Magnification, X40. (TIF)
    Preview · Dataset · May 2012
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    Dataset: Figure S4
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    ABSTRACT: Nuclear staining in normal kidney tissue. In conditions previously described, IQGAP1 labelling (green) and nuclear staining with DAPI was performed. Labelling is representative of normal kidney. Scale bar, 50 µm. Analysis was performed with a confocal microscope. Microscope sections, 0.5 µm. Magnification, X40. Nephrin staining in normal kidney tissue: In conditions previously described, nephrin labelling (red) was performed. In normal glomeruli, nephrin staining (red) was continuous around the glomerular basement membrane. Scale bar, 50 µm. Analysis was performed with a confocal microscope. Microscope sections, 0.5 µm. Magnification, X40. (TIF)
    Preview · Dataset · May 2012
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    Full-text · Chapter · Feb 2012

  • No preview · Article · Sep 2011 · Néphrologie & Thérapeutique
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    ABSTRACT: INTRODUCTION AND AIMS: The development of vascular calcification (VC) in elderly patients generates significantly increased cardiovascular risk. In patients with chronic kidney disease (CKD) the VC process occurs much more rapidly. Matrix-Gla protein (MGP) is a vitamin-K dependent protein that inhibits calcification. Warfarin, a common therapy used in dialysis patients, attenuates the activity of MGP by blocking the formation of vitamin K. In the present study we sought to determine whether a therapeutic warfarin treatment accelerated the rate of VC in a rat model of CKD. METHODS: Sprague Dawley rats were fed a diet containing either 0.25% adenine (CKD) or 0% adenine (control), both diets containing high phosphate (1%) and low vitamin K (0.2 mg/kg). Warfarin (0.1 mg/kg body weight/day) was administered in the drinking water of CKD (n=8) and control (n=8) animals. After 7 weeks on the diet, rats were anesthetized and fluid filled catheters inserted into the carotid artery were used to measure blood pressure using PowerLab data aquisition system (ADInstruments, Colarado, USA). Kidney function was assessed by measuring serum creatinine and urea. INR values were assessed using INRatio 2 (HemoSense, San Diego, CA, USA). VC was assessed using the calcium-O-cresophthalein assay. RESULTS: Creatinine levels were significantly elevated in the CKD group (345 ± 117 µmol/L) compared to controls (51 ± 10 µmol/L). Serum phosphate levels were also elevated in CKD animals (4.8 ± 2.8 mM) compared to controls (1.9 ± 0.4 mM) and linearly correlated with creatinine (r2=0.73, p<0.0001). INR levels were elevated from 1.3 ± 0.2 in controls to 3.3 ± 0.8 in warfarin treated animals. The calcium content was analyzed in the thoracic aorta, abdominal aorta, renal artery and carotid artery. The average calcium content in all these vessels was significantly elevated in warfarin treated CKD animals (445 ± 576 nmol/mg tissue) compared to untreated CKD animals (33 ± 59 nmol/mg tissue) and control animals with no CKD (6 ± 1.8 nmol/mg tissue). Pulse pressure in CKD animals with VC was significantly elevated compared to animals with no VC (p<0.01). CONCLUSIONS: Taken together, these results indicate that therapeutic warfarin treatment in a rat model of CKD accelerates the development of VC. Further studies are necessary to elucidate potential treatment targets to prevent this calcification process and evaluate the safety of potential alternative anticoagulation therapies in CKD. (Funds: KFOC, KM:CIHR, NS:CIHR).
    No preview · Article · Jun 2011 · CKJ: Clinical Kidney Journal
  • J Ripoche
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    ABSTRACT: An expansion of knowledge from basic and clinical research has highlighted the critical role of platelets in inflammation and tissue repair in addition to their established contribution to hemostasis. Activated platelets are a rich source of mediators participating to inflammation and tissue regeneration. Platelet-derived microparticles recapitulate essential platelet functions and their contribution to the pathogenesis of inflammatory diseases has been emphasized. Recent findings suggest that platelets are both friends and foes for the liver. Platelets are essential to liver regeneration, platelet-derived serotonin being critical. However platelets can also exacerbate liver damage, as in immune-mediated injury. The dual role of platelets has recently been exemplified in animal models of liver fibrosis. Platelets release profibrogenic mediators, such as CXC Chemokine Ligand 4, that is instrumental in the progression of liver fibrosis. On the other hand, thrombocytopenia aggravates liver fibrosis, an outcome linked to the downregulation of hepatic stellate cell collagen production by platelet derived hepatocyte growth factor. CD154, a key molecule in inflammation, is expressed by platelets and is a pathogenic mediator in inflammatory bowel disease. Here, we summarize some of the mechanisms linking platelets with inflammation and comment few recent articles indicating why platelets may prove to be important pathogenic mediators in liver and gastrointestinal diseases.
    No preview · Article · May 2011 · Gastroentérologie Clinique et Biologique
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    ABSTRACT: Inflammation and lipid metabolism pathways are linked, and deregulation of this interface may be critical in hepatic steatosis. The importance of the dialog between inflammatory signaling pathways and the unfolded protein response (UPR) in metabolism has been underlined. Herein, we studied the role of CD154, a key mediator of inflammation, in hepatic steatosis. To this end, Balb/c mice, wild-type or deficient in CD154 (CD154KO), were fed a diet rich in olive oil. In vitro, the effect of CD154 was studied on primary hepatocyte cultures and hepatocyte-derived cell lines. Results showed that CD154KO mice fed a diet rich in olive oil developed hepatic steatosis associated with reduced apolipoprotein B100 (apoB100) expression and decreased secretion of very low-density lipoproteins. This phenotype correlated with an altered UPR as assessed by reduced X-Box binding protein-1 (XBP1) messenger RNA (mRNA) splicing and reduced phosphorylation of eukaryotic initiation factor 2α. Altered UPR signaling in livers of CD154KO mice was confirmed in tunicamycin (TM) challenge experiments. Treatment of primary hepatocyte cultures and hepatocyte-derived cell lines with soluble CD154 increased XBP1 mRNA splicing in cells subjected to either oleic acid (OA) or TM treatment. Moreover, CD154 reduced the inhibition of apoB100 secretion by HepG2 cells grown in the presence of high concentrations of OA, an effect suppressed by XBP1 mRNA silencing and in HepG2 cells expressing a dominant negative form of inositol requiring ER-to-nucleus signaling protein-1. The control of the UPR by CD154 may represent one of the mechanisms involved in the pathophysiology of hepatic steatosis. Conclusion: Our study identifies CD154 as a new mediator of hepatic steatosis.
    Full-text · Article · Dec 2010 · Hepatology
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    ABSTRACT: Elastic fibers are composed of microfibrils containing fibrillin-1 and an elastic component, elastin. Microfibrils may not be associated with elastin. In the adult liver, fibrillin-1 and elastin are coexpressed within the stroma and portal tracts vessel walls. Fibrillin-1 is expressed alone around the bile ducts and within the Disse space. There is little work that has studied the elastic fiber organization during the fœtal liver development. Here, we studied the expression of fibrillin-1 and elastin by immunohistochemistry on 20 cases of fœtal liver. During the development of the portal tract, the two components are coexpressed on interstitial elastic fibers and within vessel walls. Fibrillin-1 is expressed alone around the bile structures during their maturation. Unlike adult liver, fibrillin-1 is expressed on thin and very irregular microfibrils within the Disse space. Our study shows that the elastic matrix development in the portal tract follows the development of the different structures, notably biliary structures. In the Disse space, microfibrils are not continuous. Their maturation may be in relation with the change of the hepatic blood flow after birth.
    Full-text · Article · Sep 2010 · Morphologie

  • No preview · Article · Mar 2010 · Journal des Maladies Vasculaires

Publication Stats

2k Citations
288.55 Total Impact Points

Institutions

  • 1995-2015
    • University of Bordeaux
      Burdeos, Aquitaine, France
  • 1997-2012
    • Université Victor Segalen Bordeaux 2
      • Institut de Santé Publique d'Epidémiologie et de Développement (ISPED)
      Burdeos, Aquitaine, France
  • 1995-2008
    • Centre Hospitalier Universitaire Rouen
      Rouen, Upper Normandy, France
  • 2005
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 2001
    • Institut National d'Hygiène du Maroc
      Rabat, Rabat-Salé-Zemmour-Zaër, Morocco
  • 1988-1993
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 1986-1988
    • University of Oxford
      • Department of Biochemistry
      Oxford, England, United Kingdom