Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/19839
Título
Chronic pancreatitis and lipomatosis are associated with defective function of ciliary genes in pancreatic ductal cells.
Autor(es)
Fecha de publicación
2016-11-15
Cita
Hum Mol Genet . 2016 ;25(22):5017-5026
Idioma
Inglés
Tipo de documento
research article
Resumen
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.
MESH
AMP-Activated Protein Kinases | Animals | Apoptosis | Cell Differentiation | Cilia | Epithelial Cells | Hepatocyte Nuclear Factor 6 | Lipomatosis | Metaplasia | Mice | Pancreas | Pancreatic Ducts | Pancreatic Neoplasms | Pancreatitis, Chronic | Protein Serine-Threonine Kinases
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