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Inhibition of hedgehog signaling ameliorates severity of chronic pancreatitis in experimental mouse models

  • 0Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, United States.
American Journal of Physiology. Gastrointestinal and Liver Physiology +

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November 5, 2024

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November 5, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Hedgehog signaling is activated in chronic pancreatitis (CP). Inhibiting this pathway with vismodegib resolves fibrosis and improves pancreatic health, suggesting a new treatment for CP.

Area Of Science

  • Gastroenterology and Hepatology
  • Fibrotic Diseases
  • Molecular Biology

Background

  • Chronic pancreatitis (CP) is a debilitating fibro-inflammatory pancreatic disease with limited therapeutic options.
  • Aberrant activation of developmental pathways, like the Hedgehog pathway, is implicated in various fibrotic conditions.
  • The role of Hedgehog signaling in CP pathogenesis and its therapeutic potential remain underexplored.

Purpose Of The Study

  • To investigate the involvement of the Hedgehog pathway in CP progression.
  • To evaluate the efficacy of Hedgehog pathway inhibition as a therapeutic strategy for CP.

Main Methods

  • CP was induced in mouse models using l-arginine or caerulein.
  • Mice received the Hedgehog pathway inhibitor vismodegib during or after disease induction.
  • Histopathological analysis and ex vivo pancreatic stellate cell activation assays were performed.

Main Results

  • Hedgehog signaling was found to be overactivated in CP.
  • Vismodegib treatment significantly improved CP-associated histopathological parameters.
  • Inhibition of Hedgehog signaling halted CP progression, resolved existing fibrosis, and reversed pancreatic stellate cell activation.

Conclusions

  • Hedgehog pathway activation contributes to CP.
  • Inhibiting the Hedgehog pathway with vismodegib demonstrates significant therapeutic potential for CP.
  • These findings support clinical trials for vismodegib as a novel treatment for chronic pancreatitis.

Keywords:

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