Animal models of biliary injury and altered bile acid metabolism.
Biochim Biophys Acta Mol Basis Dis
; 1864(4 Pt B): 1254-1261, 2018 04.
Article
em En
| MEDLINE
| ID: mdl-28709963
ABSTRACT
In the last 25years, a number of animal models, mainly rodents, have been generated with the goal to mimic cholestatic liver injuries and, thus, to provide in vivo tools to investigate the mechanisms of biliary repair and, eventually, to test the efficacy of innovative treatments. Despite fundamental limitations applying to these models, such as the distinct immune system and the different metabolism regulating liver homeostasis in rodents when compared to humans, multiple approaches, such as surgery (bile duct ligation), chemical-induced (3,5-diethoxycarbonyl-1,4-dihydrocollidine, DDC, α-naphthylisothiocyanate, ANIT), viral infections (Rhesus rotavirustype A, RRV-A), and genetic manipulation (Mdr2, Cftr, Pkd1, Pkd2, Prkcsh, Sec63, Pkhd1) have been developed. Overall, they have led to a range of liver phenotypes recapitulating the main features of biliary injury and altered bile acid metabolisms, such as ductular reaction, peribiliary inflammation and fibrosis, obstructive cholestasis and biliary dysgenesis. Although with a limited translability to the human setting, these mouse models have provided us with the ability to probe over time the fundamental mechanisms promoting cholestatic disease progression. Moreover, recent studies from genetically engineered mice have unveiled 'core' pathways that make the cholangiocyte a pivotal player in liver repair. In this review, we will highlight the main phenotypic features, the more interesting peculiarities and the different drawbacks of these mouse models. This article is part of a Special Issue entitled Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças dos Ductos Biliares
/
Ductos Biliares
/
Ácidos e Sais Biliares
/
Células Epiteliais
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Biochim Biophys Acta Mol Basis Dis
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Itália