2026-06-30T04:06:59Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/198392024-11-29T14:18:07Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Augereau, Cécile
author
Collet, Louis
author
Vargiu, Pierfrancesco
author
Guerra, Carmen
author
Ortega Jimenez, Sagrario
author
Lemaigre, Frédéric P
author
Jacquemin, Patrick
funder
Fondation contre le Cancer (Belgium)
funder
Universite catholique de Louvain
funder
Centre du Cancer (Cliniques universitaires St-Luc)
2024-06-24T09:11:32Z
2024-06-24T09:11:32Z
2016-11-15
Hum Mol Genet . 2016 ;25(22):5017-5026
10.1093/hmg/ddw332
1460-2083
Human molecular genetics
28159992
http://hdl.handle.net/20.500.12105/19839
Genetic diseases associated with defects in primary cilia are classified as ciliopathies. Pancreatic lesions and ductal cysts are found in patients with ciliopathic polycystic kidney diseases suggesting a close connection between pancreatic defects and primary cilia. Here we investigate the role of two genes whose deletion is known to cause primary cilium defects, namely Hnf6 and Lkb1, in pancreatic ductal homeostasis. We find that mice with postnatal duct-specific deletion of Hnf6 or Lkb1 show duct dilations. Cells lining dilated ducts present shorter cilia with swollen tips, suggesting defective intraciliary transport. This is associated with signs of chronic pancreatitis, namely acinar-to-ductal metaplasia, acinar proliferation and apoptosis, presence of inflammatory infiltrates, fibrosis and lipomatosis. Our data reveal a tight association between ductal ciliary defects and pancreatitis with perturbed acinar homeostasis and differentiation. Such injuries can account for the increased risk to develop pancreatic cancer in Peutz-Jeghers patients who carry LKB1 loss-of-function mutations.
eng
Chronic pancreatitis and lipomatosis are associated with defective function of ciliary genes in pancreatic ductal cells.
research article
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Chronicpancreatitisandlipomatosisareassociated_2016.pdf
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Chronicpancreatitisandlipomatosisareassociated_2016.pdf.txt