Molecular mechanisms of pancreatic myofibroblast activation in chronic pancreatitis and pancreatic ductal adenocarcinoma

Andrew Cannon, Christopher Michael Thompson, Rakesh Bhatia, Katharine Anne Armstrong, Joyce Christopher Solheim, Sushil Kumar, Surinder Kumar Batra

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations

Abstract

Pancreatic fibrosis (PF) is an essential component of the pathobiology of chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC). Activated pancreatic myofibroblasts (PMFs) are crucial for the deposition of the extracellular matrix, and fibrotic reaction in response to sustained signaling. Consequently, understanding of the molecular mechanisms of PMF activation is not only critical for understanding CP and PDAC biology but is also a fertile area of research for the development of novel therapeutic strategies for pancreatic pathologies. This review analyzes the key signaling events that drive PMF activation including, initiating signals from transforming growth factor-β1, platelet derived growth factor, as well as other microenvironmental cues, like hypoxia and extracellular matrix rigidity. Further, we discussed the intracellular signal events contributing to PMF activation, and crosstalk with different components of tumor microenvironment. Additionally, association of epidemiologically established risk factors for CP and PDAC, like alcohol intake, tobacco exposure, and metabolic factors with PMF activation, is discussed to comprehend the role of lifestyle factors on pancreatic pathologies. Overall, this analysis provides insight into the biology of PMF activation and highlights salient features of this process, which offer promising therapeutic targets.

Original languageEnglish (US)
Pages (from-to)689-703
Number of pages15
JournalJournal of Gastroenterology
Volume56
Issue number8
DOIs
StatePublished - Aug 2021

Keywords

  • Cell signaling
  • Chronic pancreatitis
  • Myofibroblast
  • Pancreatic cancer
  • Pancreatic fibrosis

ASJC Scopus subject areas

  • Gastroenterology

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