Role of parathyroid hormone-related protein signaling in chronic pancreatitis

Miriam Falzon, Vandanajay Bhatia

Research output: Contribution to journalReview article

10 Scopus citations

Abstract

Chronic pancreatitis (CP), a progressive inflammatory disease where acini are destroyed and replaced by fibrous tissue, increases the risk for pancreatic cancer. Risk factors include alcohol, smoking, and obesity. The effects of these risk factors are exacerbated in patients with mutations in genes that predispose to CP. The different environmental and genetic factors produce the same clinical phenotype; once CP develops, disease course is the same regardless of etiology. Critical questions still need to be answered to understand what modifies predisposition to develop CP in persons exposed to risk factors. We postulate that risk factors modulate endogenous pathways, with parathyroid hormone-related protein (PTHrP) signaling being one such pathway. In support, PTHrP levels are elevated in mice treated with alcohol, and in mouse models of cerulein- and pancreatic duct ligation-induced CP. Disrupting the Pthrp gene in acinar cells exerts protective effects (decreased edema, histological damage, amylase and cytokine release, and fibrosis) in these CP models. PTHrP levels are elevated in human CP. Currently, CP care lacks specific pharmacological interventions. Targeting PTHrP signaling may present a novel therapeutic strategy that inhibits pancreatic inflammation and fibrosis, especially since the risk of developing pancreatic cancer is strongly associated with duration of chronic inflammation.

Original languageEnglish (US)
Pages (from-to)1091-1108
Number of pages18
JournalCancers
Volume7
Issue number2
DOIs
StatePublished - Jun 18 2015

Keywords

  • Acinar cells
  • Alcohol
  • Cytokines
  • Extracellular matrix
  • Parathyroid hormone-related protein
  • Stellate cells

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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