TWEAK/Fn14 Signalling Regulates the Tissue Microenvironment in Chronic Pancreatitis

N Dianah B Abu Bakar; Rodrigo Carlessi; Jully Gogoi-Tiwari; Julia Köhn-Gaone; Vincent Williams; Marco Falasca; John K Olynyk; Grant A Ramm; Janina E E Tirnitz-Parker

doi:10.3390/cancers15061807

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TWEAK/Fn14 Signalling Regulates the Tissue Microenvironment in Chronic Pancreatitis

Journal article

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TWEAK/Fn14 Signalling Regulates the Tissue Microenvironment in Chronic Pancreatitis

N Dianah B Abu Bakar, Rodrigo Carlessi, Jully Gogoi-Tiwari, Julia Köhn-Gaone, Vincent Williams, Marco Falasca, John K Olynyk, Grant A Ramm and Janina E E Tirnitz-Parker

Cancers, Vol.15(6), Art. 1807

2023

DOI: https://doi.org/10.3390/cancers15061807

PMID: 36980694

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Abstract

chronic pancreatitis

inflammation

ethionine-supplemented diet

ductular proliferation

fibrosis

choline-deficient

TWEAK/Fn14 signalling

Chronic pancreatitis increases the risk of developing pancreatic cancer through the upregulation of pathways favouring proliferation, fibrosis, and sustained inflammation. We established in previous studies that the ligand tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) signals through its cognate receptor fibroblast growth factor-inducible 14 (Fn14) to regulate these underlying cellular processes in the chronic liver injury niche. However, the role of the TWEAK/Fn14 signalling pathway in pancreatic disease is entirely unknown. An analysis of publicly available datasets demonstrated that the TWEAK receptor Fn14 is upregulated in pancreatitis and pancreatic adenocarcinoma, with single cell RNA sequencing revealing pancreatic ductal cells as the main Fn14 producers. We then used choline-deficient, ethionine-supplemented (CDE) diet feeding of wildtype C57BL/6J and Fn14 knockout littermates to (a) confirm CDE treatment as a suitable model of chronic pancreatitis and (b) to investigate the role of the TWEAK/Fn14 signalling pathway in pancreatic ductal proliferation, as well as fibrotic and inflammatory cell dynamics. Our time course data obtained at three days, three months, and six months of CDE treatment reveal that a lack of TWEAK/Fn14 signalling significantly inhibits the establishment and progression of the tissue microenvironment in CDE-induced chronic pancreatitis, thus proposing the TWEAK/Fn14 pathway as a novel therapeutic target.

Details

Title: TWEAK/Fn14 Signalling Regulates the Tissue Microenvironment in Chronic Pancreatitis
Authors/Creators: N Dianah B Abu Bakar - Curtin University
Rodrigo Carlessi - Curtin University
Jully Gogoi-Tiwari - Murdoch University, School of Veterinary Medicine
Julia Köhn-Gaone - Curtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Bentley, WA 6102, Australia
Vincent Williams - Curtin University
Marco Falasca - Curtin University
John K Olynyk - Fiona Stanley Hospital
Grant A Ramm - QIMR Berghofer Medical Research Institute
Janina E E Tirnitz-Parker - Curtin University
Publication Details: Cancers, Vol.15(6), Art. 1807
Grant note: APP1087125 / National Health and Medical Research Council APP1160323 / National Health and Medical Research Council
Identifiers: 991005566469207891
Murdoch Affiliation: Murdoch University; School of Veterinary Medicine
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.102 Stem Cell Research; 1.102.1150 Hepatocyte Growth Factor
Web Of Science research areas: Oncology
ESI research areas: Clinical Medicine