Extrahepatic cholangiocyte cilia are abnormal in biliary atresia.

J Pediatr Gastroenterol Nutr

Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Published: July 2013

Objectives: Biliary atresia (BA) is a rapidly progressive form of biliary fibrosis affecting neonates. We previously reported that primary cilia on the intrahepatic cholangiocytes of patients with both syndromic and nonsyndromic BA were structurally abnormal. Our objective was to determine whether extrahepatic cholangiocytes in human biliary atresia, intrahepatic and extrahepatic cholangiocytes of rhesus rotavirus (RRV)-infected neonatal mice, and RRV-infected primary neonatal extrahepatic cholangiocytes also demonstrate ciliary abnormalities.

Methods: The livers of neonatal BALB/c mice injected with RRV that developed jaundice, human extrahepatic bile duct samples obtained at time of hepatoportoenterostomy, and RRV-infected primary neonatal cholangiocytes were stained with antibodies against acetylated α tubulin to identify primary cilia.

Results: Extrahepatic cholangiocytes from RRV-treated mice demonstrated minimal loss of primary cilia at day 3 but almost complete loss at day 8 and partial loss at day 12. No changes were seen in mouse intrahepatic bile ducts at any of the time points. In the human BA samples, primary cilia were almost completely absent from extrahepatic duct cholangiocytes. There were, however, abundant cilia in the peribiliary glands adjacent to extrahepatic ducts in the BA sample. Cilia in RRV-infected primary neonatal cholangiocytes were significantly decreased compared with controls.

Conclusions: Primary cilia are selectively lost from neonatal extrahepatic but not intrahepatic cholangiocytes after RRV infection in BALB/c mice. The cilia are also decreased in RRV-infected primary cholangiocytes and the extrahepatic ducts from human patients with BA. This suggests that ciliary abnormalities are part of the pathophysiology of BA.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696479PMC
http://dx.doi.org/10.1097/MPG.0b013e318296e525DOI Listing

Publication Analysis

Top Keywords

primary cilia
16
extrahepatic cholangiocytes
16
rrv-infected primary
16
biliary atresia
12
primary neonatal
12
extrahepatic
10
cholangiocytes
10
primary
9
cilia
8
intrahepatic cholangiocytes
8

Similar Publications

Moderate levels of folic acid benefit outcomes for cilia based neural tube defects.

Dev Biol

January 2025

Department of Molecular, Cellular and Development Biology, University of Colorado, Boulder, CO 80309. Electronic address:

Folic acid (FA) supplementation is a potent tool to reduce devastating birth defects known as neural tube defects (NTDs). Though effective, questions remain how FA achieves its protective effect and which gene mutations are sensitive to folic acid levels. We explore the relationship between FA dosage and NTD rates using NTD mouse models.

View Article and Find Full Text PDF

The widespread application of quantum dots (QDs) in recent years has raised concerns about potential environmental and human health risks. Although the toxicity of cadmium telluride quantum dots (CdTe QDs) has been partially studied, their effects on stem cells, tissue regeneration, neurodevelopment, and neurobehavioral toxicity remain unclear. This study aimed to investigate the combined toxic effects and mechanisms of CdTe QDs on planarians at the individual, tissue, cellular, and molecular levels.

View Article and Find Full Text PDF

Objective: Around 30% of people with schizophrenia are refractory to antipsychotic treatment (treatment-resistant schizophrenia). Abnormal structural neuroimaging findings, in particular volume and thickness reductions, are often described in schizophrenia. Novel biomarkers of active brain pathology such as neurofilament light chain protein are now expected to improve current understanding of psychiatric disorders, including schizophrenia.

View Article and Find Full Text PDF

Dyneins are huge motor protein complexes that are essential for cell motility, cell division, and intracellular transport. Dyneins are classified into three major subfamilies, namely cytoplasmic, intraflagellar-transport (IFT), and ciliary dyneins, based on their intracellular localization and functions. Recently, several near-atomic resolution structures have been reported for cytoplasmic/IFT dyneins.

View Article and Find Full Text PDF

CIROZ is dispensable in ancestral vertebrates but essential for left-right patterning in humans.

Am J Hum Genet

December 2024

Laboratory of Human Genetics & Therapeutics, Genome Institute of Singapore (GIS), A(∗)STAR, Singapore, Singapore; Laboratory of Human Genetics & Therapeutics, BESE, KAUST, Thuwal, Saudi Arabia; Department of Physiology, Cardiovascular Disease Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. Electronic address:

Four genes-DAND5, PKD1L1, MMP21, and CIROP-form a genetic module that has specifically evolved in vertebrate species that harbor motile cilia in their left-right organizer (LRO). We find here that CIROZ (previously known as C1orf127) is also specifically expressed in the LRO of mice, frogs, and fish, where it encodes a protein with a signal peptide followed by 3 zona pellucida N domains, consistent with extracellular localization. We report 16 individuals from 10 families with bi-allelic CIROZ inactivation variants, which cause heterotaxy with congenital heart defects.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!