Cholangiopathy and biliary fibrosis in ...
Type de document :
Compte-rendu et recension critique d'ouvrage
PMID :
Titre :
Cholangiopathy and biliary fibrosis in Cyp2c70-deficient mice are fully reversed by ursodeoxycholic acid
Auteur(s) :
de Boer, Jan [Auteur correspondant]
University Medical Center Groningen [Groningen] [UMCG]
de Vries, Hilde [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Palmiotti, Anna [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Li, Rumei [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Doestzada, Marwah [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Hoogerland, Joanne [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
Fu, Jingyuan [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
La Rose, Anouk [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Westerterp, Marit [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Mulder, Niels [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Hovingh, Milaine [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Koehorst, Martijn [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Kloosterhuis, Niels [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Wolters, Justina [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Bloks, Vincent [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Haas, Joel [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
Dombrowicz, David [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
Staels, Bart [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
van de Sluis, Bart [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Kuipers, Folkert [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
University Medical Center Groningen [Groningen] [UMCG]
de Vries, Hilde [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Palmiotti, Anna [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Li, Rumei [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Doestzada, Marwah [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Hoogerland, Joanne [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
Fu, Jingyuan [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
La Rose, Anouk [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Westerterp, Marit [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Mulder, Niels [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Hovingh, Milaine [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Koehorst, Martijn [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Kloosterhuis, Niels [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Wolters, Justina [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Bloks, Vincent [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Haas, Joel [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
Dombrowicz, David [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
Staels, Bart [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
van de Sluis, Bart [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Kuipers, Folkert [Auteur]
University Medical Center Groningen [Groningen] [UMCG]
Titre de la revue :
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
Pagination :
1045-1069
Éditeur :
Philadelphia, PA : American Gastroenterological Association, [2015]-
Date de publication :
2021
ISSN :
2352-345X
Mot(s)-clé(s) en anglais :
Bile Acids
Humanized Mouse Model
Liver
Primary Biliary Cholangitis.
Humanized Mouse Model
Liver
Primary Biliary Cholangitis.
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
Background and aims: Bile acids (BAs) aid intestinal fat absorption and exert systemic actions by receptor-mediated signaling. BA receptors have been identified as drug targets for liver diseases. Yet, differences in BA ...
Lire la suite >Background and aims: Bile acids (BAs) aid intestinal fat absorption and exert systemic actions by receptor-mediated signaling. BA receptors have been identified as drug targets for liver diseases. Yet, differences in BA metabolism between humans and mice hamper translation of pre-clinical outcomes. Cyp2c70-ablation in mice prevents synthesis of mouse/rat-specific muricholic acids (MCAs), but potential (patho)physiological consequences of their absence are unknown. We therefore assessed age- and gender-dependent effects of Cyp2c70-deficiency in mice.Methods: The consequences of Cyp2c70-deficiency were assessed in male and female mice at different ages.Results: Cyp2c70-/- mice were devoid of MCAs and showed high abundances of chenodeoxycholic and lithocholic acids. Cyp2c70-deficiency profoundly impacted microbiome composition. Bile flow and biliary BA secretion were normal in Cyp2c70-/- mice of both sexes. Yet, the pathophysiological consequences of Cyp2c70-deficiency differed considerably between sexes. Three-week old male Cyp2c70-/- mice showed high plasma BAs and transaminases, which spontaneously decreased thereafter to near-normal levels. Only mild ductular reactions were observed in male Cyp2c70-/- mice up to 8 months of age. In female Cyp2c70-/- mice, plasma BAs and transaminases remained substantially elevated with age, gut barrier function was impaired and bridging fibrosis was observed at advanced age. Addition of 0.1% ursodeoxycholic acid to the diet fully normalized hepatic and intestinal functions in female Cyp2c70-/- mice.Conclusion: Cyp2c70-/- mice show transient neonatal cholestasis and develop cholangiopathic features that progress to bridging fibrosis in females only. These consequences of Cyp2c70-deficiency are restored by treatment with UDCA, indicating a role of BA hydrophobicity in disease development.Lire moins >
Lire la suite >Background and aims: Bile acids (BAs) aid intestinal fat absorption and exert systemic actions by receptor-mediated signaling. BA receptors have been identified as drug targets for liver diseases. Yet, differences in BA metabolism between humans and mice hamper translation of pre-clinical outcomes. Cyp2c70-ablation in mice prevents synthesis of mouse/rat-specific muricholic acids (MCAs), but potential (patho)physiological consequences of their absence are unknown. We therefore assessed age- and gender-dependent effects of Cyp2c70-deficiency in mice.Methods: The consequences of Cyp2c70-deficiency were assessed in male and female mice at different ages.Results: Cyp2c70-/- mice were devoid of MCAs and showed high abundances of chenodeoxycholic and lithocholic acids. Cyp2c70-deficiency profoundly impacted microbiome composition. Bile flow and biliary BA secretion were normal in Cyp2c70-/- mice of both sexes. Yet, the pathophysiological consequences of Cyp2c70-deficiency differed considerably between sexes. Three-week old male Cyp2c70-/- mice showed high plasma BAs and transaminases, which spontaneously decreased thereafter to near-normal levels. Only mild ductular reactions were observed in male Cyp2c70-/- mice up to 8 months of age. In female Cyp2c70-/- mice, plasma BAs and transaminases remained substantially elevated with age, gut barrier function was impaired and bridging fibrosis was observed at advanced age. Addition of 0.1% ursodeoxycholic acid to the diet fully normalized hepatic and intestinal functions in female Cyp2c70-/- mice.Conclusion: Cyp2c70-/- mice show transient neonatal cholestasis and develop cholangiopathic features that progress to bridging fibrosis in females only. These consequences of Cyp2c70-deficiency are restored by treatment with UDCA, indicating a role of BA hydrophobicity in disease development.Lire moins >
Langue :
Anglais
Vulgarisation :
Non
Projet ANR :
Source :
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- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898074/pdf
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