The Role of Heparanase in the Pathogenesis of Acute Pancreatitis: A Potential Therapeutic Target

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 (...

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Autores principales:	Iyad Khamaysi, Preeti Singh, Susan Nasser, Hoda Awad, Yehuda Chowers, Edmond Sabo, Edward Hammond, Ian Gralnek, Irena Minkov, Alessandro Noseda, Neta Ilan, Israel Vlodavsky, Zaid Abassi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/eca65dac708643488e8a2f4fe63bd617
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spelling	oai:doaj.org-article:eca65dac708643488e8a2f4fe63bd6172021-12-02T12:32:20ZThe Role of Heparanase in the Pathogenesis of Acute Pancreatitis: A Potential Therapeutic Target10.1038/s41598-017-00715-62045-2322https://doaj.org/article/eca65dac708643488e8a2f4fe63bd6172017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00715-6https://doaj.org/toc/2045-2322Abstract 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.Iyad KhamaysiPreeti SinghSusan NasserHoda AwadYehuda ChowersEdmond SaboEdward HammondIan GralnekIrena MinkovAlessandro NosedaNeta IlanIsrael VlodavskyZaid AbassiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Iyad Khamaysi Preeti Singh Susan Nasser Hoda Awad Yehuda Chowers Edmond Sabo Edward Hammond Ian Gralnek Irena Minkov Alessandro Noseda Neta Ilan Israel Vlodavsky Zaid Abassi The Role of Heparanase in the Pathogenesis of Acute Pancreatitis: A Potential Therapeutic Target
description	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.
format	article
author	Iyad Khamaysi Preeti Singh Susan Nasser Hoda Awad Yehuda Chowers Edmond Sabo Edward Hammond Ian Gralnek Irena Minkov Alessandro Noseda Neta Ilan Israel Vlodavsky Zaid Abassi
author_facet	Iyad Khamaysi Preeti Singh Susan Nasser Hoda Awad Yehuda Chowers Edmond Sabo Edward Hammond Ian Gralnek Irena Minkov Alessandro Noseda Neta Ilan Israel Vlodavsky Zaid Abassi
author_sort	Iyad Khamaysi
title	The Role of Heparanase in the Pathogenesis of Acute Pancreatitis: A Potential Therapeutic Target
title_short	The Role of Heparanase in the Pathogenesis of Acute Pancreatitis: A Potential Therapeutic Target
title_full	The Role of Heparanase in the Pathogenesis of Acute Pancreatitis: A Potential Therapeutic Target
title_fullStr	The Role of Heparanase in the Pathogenesis of Acute Pancreatitis: A Potential Therapeutic Target
title_full_unstemmed	The Role of Heparanase in the Pathogenesis of Acute Pancreatitis: A Potential Therapeutic Target
title_sort	role of heparanase in the pathogenesis of acute pancreatitis: a potential therapeutic target
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/eca65dac708643488e8a2f4fe63bd617
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The Role of Heparanase in the Pathogenesis of Acute Pancreatitis: A Potential Therapeutic Target

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