ArticleLiver international : official journal of the International Association for the Study of the Liver2020
Proteostasis disturbances and endoplasmic reticulum stress contribute to polycystic liver disease: New therapeutic targets.
Article in Liver international : official journal of the International Association for the Study of the Liver, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- The instructive scar - the dynamic role of extracellular matrix in biliary pathophysiology.Disease models & mechanisms · 2026Review
- Senkyunolide A ameliorates cholestatic liver fibrosis by controlling CLCC1-mediated endoplasmic reticulum CaActa pharmacologica Sinica · 2025Article
- A TGFβ-ECM-integrin signaling axis drives structural reconfiguration of the bile duct to promote polycystic liver disease.Science translational medicine · 2023Article
- Novel α-1,3-Glucosyltransferase Variants and Their Broad Clinical Polycystic Liver Disease Spectrum.Genes · 2023Article
- Prediction of Neurodevelopmental Disorders Based on De Novo Coding Variation.Journal of autism and developmental disorders · 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
- Article
- GANAB as a Novel Biomarker in Multiple Sclerosis: Correlation with Neuroinflammation and IFI35.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Inhibition of NAE-dependent protein hyper-NEDDylation in cystic cholangiocytes halts cystogenesis in experimental models of polycystic liver disease.United European gastroenterology journal · 2021Article
- Neutrophils interact with cholangiocytes to cause cholestatic changes in alcoholic hepatitis.Gut · 2021Article
- Targeting UBC9-mediated protein hyper-SUMOylation in cystic cholangiocytes halts polycystic liver disease in experimental models.Journal of hepatology · 2021Article
- The Role of Autophagy in Gastric Cancer Chemoresistance: Friend or Foe?Frontiers in cell and developmental biology · 2020Review
- Scoping Review on Polycystic Liver Disease in PKD1/PKD2 Gene Carriers: Genetic Aspects, Pathophysiology, and Therapeutic Approaches.Journal of clinical and experimental hepatologyReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 7 institutions in 4 countries.
Funding
Abstract
BACKGROUND &
aimsPolycystic liver diseases (PLDs) are genetic disorders characterized by progressive development of multiple biliary cysts. Recently, novel PLD-causative genes, encoding for endoplasmic reticulum (ER)-resident proteins involved in protein biogenesis and transport, were identified. We hypothesized that aberrant proteostasis contributes to PLD pathogenesis, representing a potential therapeutic target.
methodsER stress was analysed at transcriptional (qPCR), proteomic (mass spectrometry), morphological (transmission electron microscopy, TEM) and functional (proteasome activity) levels in different PLD models. The effect of ER stress inhibitors [4-phenylbutyric acid (4-PBA)] and/or activators [tunicamycin (TM)] was tested in polycystic (PCK) rats and cystic cholangiocytes in vitro.
resultsThe expression levels of unfolded protein response (UPR) components were upregulated in liver tissue from PLD patients and PCK rats, as well as in primary cultures of human and rat cystic cholangiocytes, compared to normal controls. Cystic cholangiocytes showed altered proteomic profiles, mainly related to proteostasis (ie synthesis, folding, trafficking and degradation of proteins), marked enlargement of the ER lumen (by TEM) and hyperactivation of the proteasome. Notably, chronic treatment of PCK rats with 4-PBA decreased liver weight, as well as both liver and cystic volumes, of animals under baseline conditions or after TM administration compared to controls. In vitro, 4-PBA downregulated the expression (mRNA) of UPR effectors, normalized proteomic profiles related to protein synthesis, folding, trafficking and degradation and reduced the proteasome hyperactivity in cystic cholangiocytes, reducing their hyperproliferation and apoptosis.
conclusionsRestoration of proteostasis in cystic cholangiocytes with 4-PBA halts hepatic cystogenesis, emerging as a novel therapeutic strategy.
Indexed as
Identifiers
What OpenQuestion holds
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.