Phenotypic changes in mouse pancreatic stellate cell Ca2+ signaling events following activation in culture and in a disease model of pancreatitis

Jong Hak Won, Yu Zhang, Baoan D Ji, Craig D. Logsdon, David I. Yule

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The specific characteristics of intracellular Ca2+ signaling and the downstream consequences of these events were investigated in mouse pancreatic stellate cells (PSC) in culture and in situ using multiphoton microscopy in pancreatic lobules. PSC undergo a phenotypic transformation from a quiescent state to a myofibroblast-like phenotype in culture. This is believed to parallel the induction of an activated state observed in pancreatic disease such as chronic pancreatitis and pancreatic cancer. By day 7 in culture, the complement of cell surface receptors coupled to intracellular Ca2+ signaling was shown to be markedly altered. Specifically, protease-activated receptors (PAR) 1 and 2, responsive to thrombin and trypsin, respectively, and platelet-derived growth factor (PDGF) receptors were expressed only in activated PSC (aPSC). PAR-1, ATP, and PDGF receptor activation resulted in prominent nuclear Ca2+ signals. Nuclear Ca2+ signals and aPSC proliferation were abolished by expression of parvalbumin targeted to the nucleus. In pancreatic lobules, PSC responded to agonists consistent with the presence of only quiescent PSC. aPSC were observed following induction of experimental pancreatitis. In contrast, in a mouse model of pancreatic disease harboring elevated K-Ras activity in acinar cells, aPSC were present under control conditions and their number greatly increased following induction of pancreatitis. These data are consistent with nuclear Ca2+ signaling generated by agents such as trypsin and thrombin, likely present in the pancreas in disease states, resulting in proliferation of "primed" aPSC to contribute to the severity of pancreatic disease.

Original languageEnglish (US)
Pages (from-to)421-436
Number of pages16
JournalMolecular Biology of the Cell
Volume22
Issue number3
DOIs
StatePublished - Feb 1 2011
Externally publishedYes

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Pancreatic Stellate Cells
Pancreatitis
Pancreatic Diseases
PAR-1 Receptor
Platelet-Derived Growth Factor Receptors
Thrombin
Trypsin
PAR-2 Receptor
Parvalbumins
Myofibroblasts
Acinar Cells
Chronic Pancreatitis
Cell Surface Receptors
Pancreatic Neoplasms
Pancreas
Microscopy
Cell Culture Techniques
Adenosine Triphosphate
Phenotype

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Phenotypic changes in mouse pancreatic stellate cell Ca2+ signaling events following activation in culture and in a disease model of pancreatitis. / Won, Jong Hak; Zhang, Yu; Ji, Baoan D; Logsdon, Craig D.; Yule, David I.

In: Molecular Biology of the Cell, Vol. 22, No. 3, 01.02.2011, p. 421-436.

Research output: Contribution to journalArticle

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