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Preparing a Mice Model of Severe Acute Pancreatitis via a Combination of Caerulein and Lipopolysaccharide Intraperitoneal Injection
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Heparanase in Acute Pancreatitis
Iyad Khamaysi1, Dalit B Hamo-Giladi2, Zaid Abassi2,3
1Department of Gastroenterology, Advanced Endoscopy Procedures Unit, Rambam Health Care Campus, Haifa, Israel. k_iyad@rambam.health.gov.il.
Advances in Experimental Medicine and Biology
|April 11, 2020
Summary
Heparanase (Hpa) is upregulated in acute pancreatitis (AP), worsening disease severity. Inhibiting Hpa with PG545 or Ronepastat significantly reduced AP symptoms, indicating Hpa as a potential therapeutic target for this inflammatory condition.
Area of Science:
- Biochemistry
- Pathophysiology
- Gastroenterology
Background:
- Acute pancreatitis (AP) is a common gastrointestinal disease with poorly understood etiology and pathophysiology.
- Current treatments for AP are limited, highlighting the need for novel therapeutic targets.
- Heparanase (Hpa), an enzyme degrading heparan sulfate, is implicated in inflammation and cancer metastasis.
Purpose of the Study:
- To investigate the role of heparanase (Hpa) in the pathogenesis of acute pancreatitis (AP).
- To evaluate the therapeutic potential of Hpa inhibitors in an experimental model of AP.
Main Methods:
- Induction of AP in wild-type and Hpa-overexpressing transgenic mice using cerulein.
- Assessment of biochemical markers (amylase, lipase), histological changes (edema, inflammation), and immune responses (cytokines).
- Treatment of experimental AP with Hpa inhibitors (PG545, Ronepastat).
Main Results:
- Hpa expression and activity were significantly elevated in cerulein-induced AP.
- Hpa overexpression exacerbated AP manifestations, including edema, inflammation, and cytokine induction.
- Hpa inhibitors markedly attenuated the biochemical, histological, and immunological features of AP.
Conclusions:
- Heparanase (Hpa) plays a significant role in the pathogenesis of acute pancreatitis.
- Hpa inhibition represents a promising therapeutic strategy for managing AP.
- Hpa inhibitors may offer a dual benefit, with potential applications in both AP and cancer treatment.
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