A classification of ductal plate malformations based on distinct pathogenic mechanisms of biliary dysmorphogenesis.

Détails

ID Serval
serval:BIB_F94351A5C10C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A classification of ductal plate malformations based on distinct pathogenic mechanisms of biliary dysmorphogenesis.
Périodique
Hepatology
Auteur(s)
Raynaud P., Tate J., Callens C., Cordi S., Vandersmissen P., Carpentier R., Sempoux C., Devuyst O., Pierreux C.E., Courtoy P., Dahan K., Delbecque K., Lepreux S., Pontoglio M., Guay-Woodford L.M., Lemaigre F.P.
ISSN
1527-3350 (Electronic)
ISSN-L
0270-9139
Statut éditorial
Publié
Date de publication
2011
Peer-reviewed
Oui
Volume
53
Numéro
6
Pages
1959-1966
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
Ductal plate malformations (DPMs) are developmental anomalies considered to result from lack of ductal plate remodeling during bile duct morphogenesis. In mice, bile duct development is initiated by the formation of primitive ductal structures lined by two cell types, namely ductal plate cells and hepatoblasts. During ductal plate remodeling, the primitive ductal structures mature to ducts as a result from differentiation of the ductal plate cells and hepatoblasts to cholangiocytes. Here, we report this process is conserved in human fetal liver. These findings prompted us to evaluate how DPMs develop in three mouse models, namely mice with livers deficient in hepatocyte nuclear factor 6 (HNF6), HNF1β, or cystin-1 (cpk [congenital polycystic kidney] mice). Human liver from a patient with a HNF1B/TCF2 mutation, and from fetuses affected with autosomal recessive polycystic kidney disease (ARPKD) were also analyzed. Despite the epistatic relationship between HNF6, HNF1β, and cystin-1, the three mouse models displayed distinct morphogenic mechanisms of DPM. They all developed biliary cysts lined by cells with abnormal apicobasal polarity. However, the absence of HNF6 led to an early defect in ductal plate cell differentiation. In HNF1β-deficient liver, maturation of the primitive ductal structures was impaired. Normal differentiation and maturation but abnormal duct expansion was apparent in cpk mouse livers and in human fetal ARPKD.
CONCLUSION: DPM is the common endpoint of distinct defects initiated at distinct stages of bile duct morphogenesis. Our observations provide a new pathogenic classification of DPM.
Mots-clé
Animals, Bile Ducts, Intrahepatic/abnormalities, Bile Ducts, Intrahepatic/embryology, Biological Markers/metabolism, Cell Differentiation/physiology, Congenital Abnormalities/classification, Congenital Abnormalities/etiology, Disease Models, Animal, Hepatocyte Nuclear Factor 1-beta/metabolism, Hepatocyte Nuclear Factor 6/metabolism, Humans, Liver/embryology, Liver/metabolism, Membrane Proteins/metabolism, Mice, Mice, Mutant Strains, Morphogenesis/physiology, Polycystic Kidney Diseases/congenital, Polycystic Kidney Diseases/metabolism, Polycystic Kidney, Autosomal Recessive/metabolism, Polycystic Kidney, Autosomal Recessive/physiopathology
Pubmed
Web of science
Open Access
Oui
Création de la notice
29/01/2015 14:04
Dernière modification de la notice
09/05/2019 3:44
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