2026-06-30T04:06:58Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/198392024-11-29T14:18:07Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Augereau, Cécile author Collet, Louis author Vargiu, Pierfrancesco author Guerra, Carmen author Ortega Jimenez, Sagrario author Lemaigre, Frédéric P author Jacquemin, Patrick author 2016-11-15 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. 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 Chronic pancreatitis and lipomatosis are associated with defective function of ciliary genes in pancreatic ductal cells.