Upregulation of ELP3 in acinar cells during acute pancreatitis is dispensable for homeostasis, inflammation, regeneration, and cancer initiation. - 2025
[en] Pancreatitis, or inflammation of the pancreas, is a common gastrointestinal condition. While often acute and self-resolving, it can become chronic and promote pancreatic ductal adenocarcinoma (PDAC), the third deadliest cancer worldwide. Pancreatitis is accompanied by morphological and molecular changes, notably immune cell infiltration, fibrosis, and acinar-to-ductal metaplasia (ADM). ELP3, the catalytic subunit of the Elongator complex, modifies wobble uridine tRNAs to optimize codon translation rates. It is critical to inflammatory processes and cancer in multiple organ systems, yet its role in the pancreas has not been investigated. This study aimed to investigate the expression and implication of ELP3 during pancreatitis induced in mice via repetitive caerulein injections. Acute pancreatitis was accompanied by increased expression of ELP3, which was mainly detected in pancreatic epithelial cells. To assess its function, we genetically inactivated Elp3 in pancreatic epithelial cells. Elp3 deficiency had no detectable effects on pancreas homeostasis, on the initiation and resolution of acute pancreatitis, on the development of chronic pancreatitis, or on pancreatitis-induced PDAC initiation. Our findings indicate that ELP3 is dispensable in pancreatic formation, inflammation and PDAC initiation. Future studies should explore its role in non-epithelial cells and its potential involvement in other PDAC hallmarks, such as therapy resistance.
Disciplines :
Oncology
Author, co-author :
Aajja, Elias ; Cell Biology Unit, de Duve Institute, Université Catholique de Louvain, 1200, Woluwé-Saint-Lambert, Belgium. elias.aajja@uclouvain.be
Lefort, Hélène ; Cell Biology Unit, de Duve Institute, Université Catholique de Louvain, 1200, Woluwé-Saint-Lambert, Belgium
Mahibullah, Siam; Cell Biology Unit, de Duve Institute, Université Catholique de Louvain, 1200, Woluwé-Saint-Lambert, Belgium
Aney, Katherine J; Biological and Biomedical Sciences Program, Harvard Medical School, Boston, MA, USA ; Health Sciences and Technology Program, Harvard-MIT, Boston, MA, USA ; Genetics Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA ; Dana-Farber Cancer Institute, Boston, MA, USA
Nissim, Sahar ; Biological and Biomedical Sciences Program, Harvard Medical School, Boston, MA, USA ; Health Sciences and Technology Program, Harvard-MIT, Boston, MA, USA ; Genetics Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA ; Dana-Farber Cancer Institute, Boston, MA, USA ; Gastroenterology Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
Nguyen, Laurent ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques ; Walloon Excellence in Life Sciences and Biotechnology, WEL Research Institute, 1300, Wavre, Belgium
Chariot, Alain ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale ; Walloon Excellence in Life Sciences and Biotechnology, WEL Research Institute, 1300, Wavre, Belgium
Henriet, Patrick ; Cell Biology Unit, de Duve Institute, Université Catholique de Louvain, 1200, Woluwé-Saint-Lambert, Belgium
Tyteca, Donatienne ; Cell Biology Unit, de Duve Institute, Université Catholique de Louvain, 1200, Woluwé-Saint-Lambert, Belgium
Close, Pierre ; Université de Liège - ULiège > Département de pharmacie
Pierreux, Christophe E ; Cell Biology Unit, de Duve Institute, Université Catholique de Louvain, 1200, Woluwé-Saint-Lambert, Belgium. christophe.pierreux@uclouvain.be
Language :
English
Title :
Upregulation of ELP3 in acinar cells during acute pancreatitis is dispensable for homeostasis, inflammation, regeneration, and cancer initiation.
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