Generation of Hydrogen Peroxide and Downstream Protein Kinase D1 Signaling Is a Common Feature of Inducers of Pancreatic Acinar-to-Ductal Metaplasia

Heike R. Döppler, Geou Yarh Liou, Peter Storz

Research output: Contribution to journalArticlepeer-review

Abstract

Pancreatic acinar-to-ductal metaplasia (ADM) is a reversible process that occurs after pancreatic injury, but becomes permanent and leads to pancreatic lesions in the presence of an oncogenic mutation in KRAS. While inflammatory macrophage-secreted chemokines, growth factors that activate epidermal growth factor receptor (EGFR) and oncogenic KRAS have been implicated in the induction of ADM, it is currently unclear whether a common underlying signaling mechanism exists that drives this process. In this study, we show that different inducers of ADM increase levels of hydrogen peroxide, most likely generated at the mitochondria, and upregulate the expression of Protein Kinase D1 (PKD1), a kinase that can be activated by hydrogen peroxide. PKD1 expression in acinar cells affects their survival and mediates ADM, which is in part due to the PKD1 target NFκB. Overall, our data implicate ROS-PKD1 signaling as a common feature of different inducers of pancreatic ADM.

Original languageEnglish (US)
Article number137
JournalAntioxidants
Volume11
Issue number1
DOIs
StatePublished - Jan 2022

Keywords

  • ADM
  • Acinar-to-ductal metaplasia
  • Hydrogen peroxide
  • Oxidative stress
  • PKD
  • Pancreas
  • Protein Kinase D

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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