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

Publisher: Springer International Country of Publication: Japan NLM ID: 9430794 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1435-5922 (Electronic) Linking ISSN: 09441174 NLM ISO Abbreviation: J Gastroenterol Subsets: MEDLINE

Original Publication: Tokyo : Springer International, c1994-

Carcinoma, Pancreatic Ductal/*genetics ; Myofibroblasts/*drug effects ; Pancreatitis, Chronic/*physiopathology; Carcinoma, Pancreatic Ductal/physiopathology ; Humans ; Pancreas/pathology ; Pancreatitis, Chronic/genetics ; Signal Transduction/drug effects ; Signal Transduction/genetics

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.
(© 2021. Japanese Society of Gastroenterology.)

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Keywords: Cell signaling; Chronic pancreatitis; Myofibroblast; Pancreatic cancer; Pancreatic fibrosis

Date Created: 20210719 Date Completed: 20211203 Latest Revision: 20220802

20250114

PMC9052363

10.1007/s00535-021-01800-4

34279724