Abstract
Cholangiocytes are the targets of several liver diseases termed cholangiopathies that result in cholestasis and the development of hepatic fibrosis and carcinogenesis. There are numerous studies investigating the role of cholangiocyte death during the progression of cholangiopathies to end-stage liver disease. This chapter reviews the pathophysiology of primary sclerosing cholangitis, primary biliary cholangitis, autosomal dominant polycystic kidney disease, and biliary atresia. We will also discuss current animal models used to study these cholangiopathies and review the mechanisms of cell death in these disease processes, including the roles of innate immune system, apoptosis, senescence, autophagy, and lipoapoptosis. A thorough understanding of cholangiocyte death during cholestatic liver disease is critical to develop targeted therapies against these disease processes.
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Abbreviations
- ADPKD:
-
Autosomal dominant polycystic kidney disease
- AEA:
-
Anandamide
- AKT:
-
Protein kinase B
- AMA:
-
Antimitochondrial antibodies
- BA:
-
Biliary atresia
- BDL:
-
Bile duct ligation
- CBDL:
-
Common bile duct ligation
- CCA:
-
Cholangiocarcinoma
- CD:
-
Cluster of differentiation
- DEN:
-
Diethylnitrosamine
- FADD:
-
Fas-associated death domain
- FFA:
-
Free fatty acid
- HSC:
-
Hepatic stellate cells
- IFN-γ:
-
Interferon- γ
- IL:
-
Interleukin
- JNK:
-
c-Jun N-terminal kinase
- LMBDL:
-
Left median bile duct ligation
- NAFLD:
-
Nonalcoholic fatty liver disease
- NF-kB:
-
Nuclear factor kappa-light-chain-enhancer of activated B cells
- NK:
-
Natural killer
- NOD:
-
Nucleotide-binding oligomerization domain
- PAMPs:
-
Pathogen-associated molecular patterns
- pANCA:
-
Peri-neutrophil cytoplasmic antibody
- PBC:
-
Primary biliary cholangitis
- PKD:
-
Polycystic kidney disease
- PNPLA3:
-
Patatin-like phospholipase domain-containing protein 3
- PRR:
-
Pattern-recognition receptors
- PSC:
-
Primary sclerosing cholangitis
- PUMA:
-
p53 upregulated modulator of apoptosis
- STAT3:
-
Signal transducer and activator of transcription 3
- TLRs:
-
Toll-like receptors
- TNF:
-
Tumor necrosis factor
- TRAIL:
-
Tumor necrosis factor-related apoptosis-inducing ligand
- UDCA:
-
Ursodeoxycholic acid
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O’Brien, A. et al. (2017). The Role of Cholangiocyte Cell Death in the Development of Biliary Diseases. In: Ding, WX., Yin, XM. (eds) Molecules, Systems and Signaling in Liver Injury. Cell Death in Biology and Diseases. Springer, Cham. https://doi.org/10.1007/978-3-319-58106-4_2
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