4 results on '"Thirard, Steeve"'
Search Results
2. Cross talk between Paneth and tuft cells drives dysbiosis and inflammation in the gut mucosa.
- Author
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Coutry, Nathalie, Nguyen, Julie, Soualhi, Salima, Gerbe, François, Meslier, Victoria, Dardalhon, Valérie, Almeida, Mathieu, Quinquis, Benoit, Thirion, Florence, Herbert, Fabien, Gasmi, Imène, Lamrani, Ali, Giordano, Alicia, Cesses, Pierre, Garnier, Laure, Thirard, Steeve, Greuet, Denis, Cazevieille, Chantal, Bernex, Florence, and Bressuire, Christelle
- Subjects
DYSBIOSIS ,MUCOUS membranes ,GUT microbiome ,GASTROINTESTINAL system ,INFLAMMATION - Abstract
Gut microbiota imbalance (dysbiosis) is increasingly associated with pathological conditions, both within and outside the gastrointestinal tract. Intestinal Paneth cells are considered to be guardians of the gut microbiota, but the events linking Paneth cell dysfunction with dysbiosis remain unclear. We report a three-step mechanism for dysbiosis initiation. Initial alterations in Paneth cells, as frequently observed in obese and inflammatorybowel diseases patients, cause a mild remodeling of microbiota, with amplification of succinate-producing species. SucnR1 -dependent activation of epithelial tuft cells triggers a type 2 immune response that, in turn, aggravates the Paneth cell defaults, promoting dysbiosis and chronic inflammation. We thus reveal a function of tuft cells in promoting dysbiosis following Paneth cell deficiency and an unappreciated essential role of Paneth cells in maintaining a balanced microbiota to prevent inappropriate activation of tuft cells and deleterious dysbiosis. This succinate--tuft cell inflammation circuit may also contribute to the chronic dysbiosis observed in patients. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
3. Genetic Ablation of G Protein-Gated Inwardly Rectifying K+ Channels Prevents Training-Induced Sinus Bradycardia.
- Author
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Bidaud, Isabelle, D'Souza, Alicia, Forte, Gabriella, Torre, Eleonora, Greuet, Denis, Thirard, Steeve, Anderson, Cali, Chung You Chong, Antony, Torrente, Angelo G., Roussel, Julien, Wickman, Kevin, Boyett, Mark R., Mangoni, Matteo E., and Mesirca, Pietro
- Subjects
BRADYCARDIA ,SINOATRIAL node ,SWIMMERS ,SWIMMING training ,MESSENGER RNA ,POTASSIUM channels ,WESTERN diet - Abstract
Background: Endurance athletes are prone to bradyarrhythmias, which in the long-term may underscore the increased incidence of pacemaker implantation reported in this population. Our previous work in rodent models has shown training-induced sinus bradycardia to be due to microRNA (miR)-mediated transcriptional remodeling of the HCN4 channel, leading to a reduction of the "funny" (I
f ) current in the sinoatrial node (SAN). Objective: To test if genetic ablation of G-protein-gated inwardly rectifying potassium channel, also known as IKACh channels prevents sinus bradycardia induced by intensive exercise training in mice. Methods: Control wild-type (WT) and mice lacking GIRK4 (Girk4–/– ), an integral subunit of IKACh were assigned to trained or sedentary groups. Mice in the trained group underwent 1-h exercise swimming twice a day for 28 days, 7 days per week. We performed electrocardiogram recordings and echocardiography in both groups at baseline, during and after the training period. At training cessation, mice were euthanized and SAN tissues were isolated for patch clamp recordings in isolated SAN cells and molecular profiling by quantitative PCR (qPCR) and western blotting. Results: At swimming cessation trained WT mice presented with a significantly lower resting HR that was reversible by acute IKACh block whereas Girk4–/– mice failed to develop a training-induced sinus bradycardia. In line with HR reduction, action potential rate, density of If , as well as of T- and L-type Ca2+ currents (ICaT and ICaL ) were significantly reduced only in SAN cells obtained from WT-trained mice. If reduction in WT mice was concomitant with downregulation of HCN4 transcript and protein, attributable to increased expression of corresponding repressor microRNAs (miRs) whereas reduced ICaL in WT mice was associated with reduced Cav 1.3 protein levels. Strikingly, IKACh ablation suppressed all training-induced molecular remodeling observed in WT mice. Conclusion: Genetic ablation of cardiac IKACh in mice prevents exercise-induced sinus bradycardia by suppressing training induced remodeling of inward currents If , ICaT and ICaL due in part to the prevention of miR-mediated transcriptional remodeling of HCN4 and likely post transcriptional remodeling of Cav 1.3. Strategies targeting cardiac IKACh may therefore represent an alternative to pacemaker implantation for bradyarrhythmias seen in some veteran athletes. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
4. Genetic Ablation of G Protein-Gated Inwardly Rectifying K + Channels Prevents Training-Induced Sinus Bradycardia.
- Author
-
Bidaud I, D'Souza A, Forte G, Torre E, Greuet D, Thirard S, Anderson C, Chung You Chong A, Torrente AG, Roussel J, Wickman K, Boyett MR, Mangoni ME, and Mesirca P
- Abstract
Background: Endurance athletes are prone to bradyarrhythmias, which in the long-term may underscore the increased incidence of pacemaker implantation reported in this population. Our previous work in rodent models has shown training-induced sinus bradycardia to be due to microRNA (miR)-mediated transcriptional remodeling of the HCN4 channel, leading to a reduction of the "funny" ( I
f ) current in the sinoatrial node (SAN). Objective: To test if genetic ablation of G-protein-gated inwardly rectifying potassium channel, also known as IKACh channels prevents sinus bradycardia induced by intensive exercise training in mice. Methods: Control wild-type (WT) and mice lacking GIRK4 ( Girk4-/- ), an integral subunit of IKACh were assigned to trained or sedentary groups. Mice in the trained group underwent 1-h exercise swimming twice a day for 28 days, 7 days per week. We performed electrocardiogram recordings and echocardiography in both groups at baseline, during and after the training period. At training cessation, mice were euthanized and SAN tissues were isolated for patch clamp recordings in isolated SAN cells and molecular profiling by quantitative PCR (qPCR) and western blotting. Results: At swimming cessation trained WT mice presented with a significantly lower resting HR that was reversible by acute IKACh block whereas Girk4-/- mice failed to develop a training-induced sinus bradycardia. In line with HR reduction, action potential rate, density of If , as well as of T- and L-type Ca2+ currents ( ICaT and ICaL ) were significantly reduced only in SAN cells obtained from WT-trained mice. If reduction in WT mice was concomitant with downregulation of HCN4 transcript and protein, attributable to increased expression of corresponding repressor microRNAs (miRs) whereas reduced ICaL in WT mice was associated with reduced Cav 1.3 protein levels. Strikingly, IKACh ablation suppressed all training-induced molecular remodeling observed in WT mice. Conclusion: Genetic ablation of cardiac IKACh in mice prevents exercise-induced sinus bradycardia by suppressing training induced remodeling of inward currents If , ICaT and ICaL due in part to the prevention of miR-mediated transcriptional remodeling of HCN4 and likely post transcriptional remodeling of Cav 1.3. Strategies targeting cardiac IKACh may therefore represent an alternative to pacemaker implantation for bradyarrhythmias seen in some veteran athletes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bidaud, D’Souza, Forte, Torre, Greuet, Thirard, Anderson, Chung You Chong, Torrente, Roussel, Wickman, Boyett, Mangoni and Mesirca.)- Published
- 2021
- Full Text
- View/download PDF
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