ArticleHepatology (Baltimore, Md.)2018
Cholangiocyte autophagy contributes to hepatic cystogenesis in polycystic liver disease and represents a potential therapeutic target.
Article in Hepatology (Baltimore, Md.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Targeting of a Bile Acid Receptor, Takeda G Protein Receptor 5 [TGR5], by a Novel First-in-Class Competitive Antagonist, SBI-364, Diminishes Hepatic and Renal Cystogenesis in Polycystic Liver and Kidney Disease.ACS pharmacology & translational science · 2025Article
- Clinical manifestation, epidemiology, genetic basis, potential molecular targets, and current treatment of polycystic liver disease.Orphanet journal of rare diseases · 2024Review
- Novel α-1,3-Glucosyltransferase Variants and Their Broad Clinical Polycystic Liver Disease Spectrum.Genes · 2023Article
- Genetics, pathobiology and therapeutic opportunities of polycystic liver disease.Nature reviews. Gastroenterology & hepatology · 2022Review
- Polycystic Liver Disease: Advances in Understanding and Treatment.Annual review of pathology · 2022Review
- Polycystic Liver Disease: Pathophysiology, Diagnosis and Treatment.Hepatic medicine : evidence and research · 2022Review
- Autophagy-mediated reduction of miR-345 contributes to hepatic cystogenesis in polycystic liver disease.JHEP reports : innovation in hepatology · 2021Article
- Proteostasis disturbances and endoplasmic reticulum stress contribute to polycystic liver disease: New therapeutic targets.Liver international : official journal of the International Association for the Study of the Liver · 2020Article
- HDAC6-dependent ciliophagy is involved in ciliary loss and cholangiocarcinoma growth in human cells and murine models.American journal of physiology. Gastrointestinal and liver physiology · 2020Article
- The HOPS complex subunit VPS39 controls ciliogenesis through autophagy.Human molecular genetics · 2020Article
- Apoptosis and autophagy in polycystic kidney disease (PKD).Cellular signalling · 2020Review
- Polycystic liver disease: Classification, diagnosis, treatment process, and clinical management.World journal of hepatology · 2020Review
- The management of polycystic liver disease by tolvaptan.Clinical and molecular hepatology · 2020Article
- Review
- Pathobiology of inherited biliary diseases: a roadmap to understand acquired liver diseases.Nature reviews. Gastroenterology & hepatology · 2019Review
- The Role of Autophagy in Liver Epithelial Cells and Its Impact on Systemic Homeostasis.Nutrients · 2019Review
- Wnt-β-catenin signalling in liver development, health and disease.Nature reviews. Gastroenterology & hepatology · 2019Review
- Effect of Trehalose Supplementation on Autophagy and Cystogenesis in a Mouse Model of Polycystic Kidney Disease.Nutrients · 2018Article
- Combination of a Histone Deacetylase 6 Inhibitor and a Somatostatin Receptor Agonist Synergistically Reduces Hepatorenal Cystogenesis in an Animal Model of Polycystic Liver Disease.The American journal of pathology · 2018Article
- Dorsal Root Ganglion Maintains Stemness of Bone Marrow Mesenchymal Stem Cells by Enhancing Autophagy through the AMPK/mTOR Pathway in a Coculture System.Stem cells international · 2018Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Polycystic liver disease (PLD) is a group of genetic disorders with limited treatment options and significant morbidity. Hepatic cysts arise from cholangiocytes exhibiting a hyperproliferative phenotype. Considering that hyperproliferation of many cell types is associated with alterations in autophagy, we hypothesized that autophagy is altered in PLD cholangiocytes, contributes to hepatic cystogenesis, and might represent a potential therapeutic target. We employed functional pathway cluster analysis and next-generation sequencing, transmission electron microscopy, immunofluorescence confocal microscopy, and western blotting to assess autophagy in human and rodent PLD cholangiocytes. A three-dimensional culture model was used to study the effects of molecular and pharmacologic inhibition of autophagy on hepatic cystogenesis in vitro, and the polycystic kidney disease-specific rat, an animal model of PLD, to study the effects of hydroxychloroquine, a drug that interferes with the autophagy pathway, on disease progression in vivo. Assessment of the transcriptome of PLD cholangiocytes followed by functional pathway cluster analysis revealed that the autophagy-lysosomal pathway is one of the most altered pathways in PLD. Direct evaluation of autophagy in PLD cholangiocytes both in vitro and in vivo showed increased number and size of autophagosomes, lysosomes, and autolysosomes; overexpression of autophagy-related proteins (Atg5, Beclin1, Atg7, and LC3); and enhanced autophagic flux associated with activation of the cAMP-protein kinase A-cAMP response element-binding protein signaling pathway. Molecular and pharmacologic intervention in autophagy with ATG7 small interfering RNA, bafilomycin A
conclusionAutophagy is increased in PLD cholangiocytes, contributes to hepatic cystogenesis, and represents a potential therapeutic target for disease treatment. (Hepatology 2018;67:1088-1108).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.