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The Role of Heparanase in the Pathogenesis of Acute Pancreatitis: A Potential Therapeutic Target.
- Source :
-
Scientific reports [Sci Rep] 2017 Apr 06; Vol. 7 (1), pp. 715. Date of Electronic Publication: 2017 Apr 06. - Publication Year :
- 2017
-
Abstract
- Acute pancreatitis (AP) is one of the most common diseases in gastroenterology. However, neither the etiology nor the pathophysiology of the disease is fully understood and no specific or effective treatment has been developed. Heparanase is an endoglycosidase that cleaves heparan sulfate (HS) side chains of HS sulfate proteoglycans into shorter oligosaccharides, activity that is highly implicated in cellular invasion associated with cancer metastasis and inflammation. Given that AP involves a strong inflammatory aspect, we examined whether heparanase plays a role in AP. Here, we provide evidence that pancreatic heparanase expression and activity are significantly increased following cerulein treatment. Moreover, pancreas edema and inflammation, as well as the induction of cytokines and signaling molecules following cerulein treatment were attenuated markedly by heparanase inhibitors, implying that heparanase plays a significant role in AP. Notably, all the above features appear even more pronounced in transgenic mice over expressing heparanase, suggesting that these mice can be utilized as a sensitive model system to reveal the molecular mechanism by which heparanase functions in AP. Heparanase, therefore, emerges as a potential new target in AP, and heparanase inhibitors, now in phase I/II clinical trials in cancer patients, are hoped to prove beneficial also in AP.
- Subjects :
- Acute Disease
Animals
Cathepsin L genetics
Cathepsin L metabolism
Ceruletide adverse effects
Disease Models, Animal
Disease Susceptibility
Enzyme Activation
Gene Expression
Humans
Immunohistochemistry
Mice
Mice, Transgenic
NF-kappa B metabolism
Neutrophil Infiltration
Neutrophils immunology
Neutrophils metabolism
Neutrophils pathology
Pancreas metabolism
Pancreas pathology
Pancreas ultrastructure
Pancreatitis pathology
STAT3 Transcription Factor metabolism
Glucuronidase genetics
Glucuronidase metabolism
Pancreatitis etiology
Pancreatitis metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 7
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 28386074
- Full Text :
- https://doi.org/10.1038/s41598-017-00715-6