Papers by Nathalie Vergnolle
Gastroenterology, May 1, 2023
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Gastroenterology, May 1, 2023
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The FASEB Journal, Apr 1, 2020
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Parasite Immunology, Sep 27, 2017
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Neurogastroenterology and Motility, Jul 11, 2017
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Journal of Crohn's and Colitis, Feb 22, 2020
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Nature Communications, Mar 13, 2019
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The FASEB Journal, Apr 1, 2020
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European Neuropsychopharmacology, Oct 1, 2017
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European Journal of Pain, Nov 6, 2015
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The FASEB Journal, 2006
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Cancer Research, 2007
3091 Tissue kallikreins (KLKs) comprise a family of secreted serine proteinases that are up-regul... more 3091 Tissue kallikreins (KLKs) comprise a family of secreted serine proteinases that are up-regulated in a variety of cancers and are highly expressed at sites of inflammation. For example, KLKs 5, 6 and 14 are found at increased levels in the serum and/or ascites fluid of ovarian and breast cancer patients and KLK6 can be detected within multiple sclerosis lesions. Despite their widespread expression in normal and diseased tissues, the mechanisms whereby these enzymes regulate cellular function are not clear. We have recently shown that kallikreins can activate proteinase activated receptors (PARs), a family of G-protein coupled cell surface receptors. PARs have been associated with inflammation, having either an anti- or pro-inflammatory role in different pathological settings. We hypothesised that like trypsin and thrombin, one of the kallikreins, KLK14, can trigger an inflammatory response by activating the members of the PAR family. We, therefore, studied the ability of kallikr...
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Nature Reviews Gastroenterology & Hepatology, 2021
Microorganisms colonize various ecological niches in the human habitat, as they do in nature. Pre... more Microorganisms colonize various ecological niches in the human habitat, as they do in nature. Predominant forms of multicellular communities called biofilms colonize human tissue surfaces. The gastrointestinal tract is home to a profusion of microorganisms with intertwined, but not identical, lifestyles: as isolated planktonic cells, as biofilms and in biofilm-dispersed form. It is therefore of major importance in understanding homeostatic and altered host–microorganism interactions to consider not only the planktonic lifestyle, but also biofilms and biofilm-dispersed forms. In this Review, we discuss the natural organization of microorganisms at gastrointestinal surfaces, stratification of microbiota taxonomy, biogeographical localization and trans-kingdom interactions occurring within the biofilm habitat. We also discuss existing models used to study biofilms. We assess the contribution of the host–mucosa biofilm relationship to gut homeostasis and to diseases. In addition, we describe how host factors can shape the organization, structure and composition of mucosal biofilms, and how biofilms themselves are implicated in a variety of homeostatic and pathological processes in the gut. Future studies characterizing biofilm nature, physical properties, composition and intrinsic communication could shed new light on gut physiology and lead to potential novel therapeutic options for gastrointestinal diseases. In this Review, Motta, Vergnolle and colleagues describe the organization of microorganisms into planktonic, biofilm and biofilm-dispersed forms in the gastrointestinal tract. The role of the host–biofilm relationship in gut homeostasis and disease is discussed. Bacteria adopt different lifestyles in their natural habitats, from single planktonic cells to biofilm communities. Polymicrobial biofilms naturally grow throughout the gastrointestinal tract, both at the epithelial surface and in the lumen as mucin-attached and food particle-attached colonies. The biofilm lifestyle influences metabolic behaviour of the microbiota but more research is needed to characterize gut biofilm-specific metabolites and their effects on the host response in health and disease. Polymicrobial and trans-kingdom interactions occur in gut biofilms; deciphering the nature of such interactions might improve our current understanding of the homeostatic relationship between the host and its gut microbiota. Abnormal biofilm features are associated with gastrointestinal diseases; characterization of biofilm alterations and cause-to-effect studies are warranted to elucidate their role in pathophysiology. Investigating biogeographical redistribution of biofilms at mucosal surfaces might provide new tools to characterize microbial alterations associated with gastrointestinal diseases and options for therapeutic intervention. Bacteria adopt different lifestyles in their natural habitats, from single planktonic cells to biofilm communities. Polymicrobial biofilms naturally grow throughout the gastrointestinal tract, both at the epithelial surface and in the lumen as mucin-attached and food particle-attached colonies. The biofilm lifestyle influences metabolic behaviour of the microbiota but more research is needed to characterize gut biofilm-specific metabolites and their effects on the host response in health and disease. Polymicrobial and trans-kingdom interactions occur in gut biofilms; deciphering the nature of such interactions might improve our current understanding of the homeostatic relationship between the host and its gut microbiota. Abnormal biofilm features are associated with gastrointestinal diseases; characterization of biofilm alterations and cause-to-effect studies are warranted to elucidate their role in pathophysiology. Investigating biogeographical redistribution of biofilms at mucosal surfaces might provide new tools to characterize microbial alterations associated with gastrointestinal diseases and options for therapeutic intervention.
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Bioorganic Chemistry, 2020
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Brain, Behavior, and Immunity, 2019
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Gastroenterology, Jan 18, 2016
For decades, interactions between the enteric neuromuscular apparatus and the central nervous sys... more For decades, interactions between the enteric neuromuscular apparatus and the central nervous system have served as the primary focus of pathophysiological research in the functional gastrointestinal disorders. The accumulation of patient reports, as well as clinical observations, has belatedly led to an interest in the role of various luminal factors and their interactions with each other and the host in functional gastrointestinal disorders. Most prominent among these factors has been the role of food. As a consequence, while not always evidence-based, dietary interventions are enjoying a renaissance in irritable bowel syndrome management. Not surprisingly, given its exploration in many disease states, the gut microbiota has also been studied in functional gastrointestinal disorders; data remain inconclusive. Likewise, there is also a considerable body of experimental and some clinical data to link functional gastrointestinal disorders pathogenesis to disturbances in epithelial ba...
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Background and purpose Chymotrypsin is a serine protease produced by the pancreas and secreted in... more Background and purpose Chymotrypsin is a serine protease produced by the pancreas and secreted into the lumen of the small intestine, where it digests food proteins. Due to its presence in the gut lumen, we hypothesized that chymotrypsin activity may be found close to epithelial cells and signals to them via Protease-activated receptors (PARs). We deciphered molecular pharmacology mechanisms for chymotrypsin signaling in intestinal epithelial cells. Experimental approaches The presence and activity of chymotrypsin were evaluated by western blot (WB) and enzymatic activity tests in luminal and mucosal compartments of murine and human gut samples. The ability of chymotrypsin to cleave the extracellular domain of PAR1 or PAR2 was assessed using cell lines expressing N-terminally-tagged receptors. The cleavage site of chymotrypsin on PAR1 and PAR2 was determined by HPLC-MS analysis. To study the pharmacology of chymotrypsin signals, we investigated calcium signaling and ERK1/2 activatio...
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HAL (Le Centre pour la Communication Scientifique Directe), 2004
Activation of colonic proteinase-activated receptor-2 (PAR(2)) caused inflammation and increased ... more Activation of colonic proteinase-activated receptor-2 (PAR(2)) caused inflammation and increased mucosal permeability in mouse colon. The present study was aimed at characterizing the possible links between these two phenomena. We evaluated the effects of intracolonic infusion of PAR(2)-activating peptide, SLIGRL, on colonic paracellular permeability and inflammation at two different doses, 5 and 100 microg per mouse, in an attempt to discriminate between both PAR(2)-mediated effects. We further investigated the possible involvement of interferon gamma (IFN-gamma) and calmodulin-dependent activation of myosin light chain kinase (MLCK), and alterations of zonula occludens-1 (ZO-1) localization in PAR(2)-induced responses. Thus, at the lower dose, SLIGRL increased colonic permeability without causing inflammation. Western blotting showed phosphorylation of mucosal myosin light chain (MLC) expression after both doses of SLIGRL. Moreover, while the MLCK inhibitor, ML-7, abolished the permeability effects of the low dose of SLIGRL, it only partially inhibited that of the high dose. In IFN-gamma-deficient mice (B6 ifng(-/-)), the increases in permeability were similar for both doses of SLIGRL and prevented by ML-7. In addition, MLCK immunoprecipitation revealed an increase of calmodulin binding to MLCK in the mucosa of mice treated with either dose of SLIGRL. Finally, we have shown that direct activation of PAR(2) on enterocytes is responsible for increased permeability and ZO-1 disruption. Moreover, SLIGRL at a dose that does not produce inflammation increases permeability via calmodulin activation, which binds and activates MLCK. The resulting tight junction opening does not depend upon IFN-gamma secretion, while the increased permeability in response to the high dose of PAR(2) agonist involves IFN-gamma secretion.
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American Journal of Physiology-gastrointestinal and Liver Physiology, Dec 1, 2022
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Papers by Nathalie Vergnolle