Pancreatic stellate cells: what's new?

Pang, Tony; Wilson, Jeremy S.; Apte, Minoti V.

doi:10.1097/mog.0000000000000378

Cited by 38 publications

(34 citation statements)

References 60 publications

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“…The role of these cells in normal physiology is unclear, but they have long been suspected of contributing to the fibrosis occurring in chronic pancreatitis as well as pancreatic cancer (Ferdek & Jakubowska, ; Pang et al . ). In the normal pancreas, PSCs can be observed as thin elongated structures situated at the acinar periphery, very close to the basal surface of the PACs (Gryshchenko et al .…”

Section: Introductionmentioning

confidence: 97%

“…More recently, Ca 2+ signalling and ion channels have been studied in pancreatic stellate cells (PSCs) (Fels et al 2016;Ferdek et al 2016;Gryshchenko et al 2016;Nielsen et al 2017;Storck et al 2017). The role of these cells in normal physiology is unclear, but they have long been suspected of contributing to the fibrosis occurring in chronic pancreatitis as well as pancreatic cancer (Ferdek & Jakubowska, 2017;Pang et al 2017). In the normal pancreas, PSCs can be observed as thin elongated structures situated at the acinar periphery, very close to the basal surface of the PACs .…”

Section: Introductionmentioning

confidence: 99%

“…PSCs can undergo significant transformations and this occurs in pancreatitis (Ferdek & Jakubowska, 2017;Pang et al 2017), but it is not known how this would affect Ca 2+ signal generation in PSCs in response to various stimuli.…”

Section: Introductionmentioning

confidence: 99%

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Calcium signalling in the acinar environment of the exocrine pancreas: physiology and pathophysiology

Gryshchenko

Gerasimenko

Peng

et al. 2018

The Journal of Physiology

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Key points Ca2+ signalling in different cell types in exocrine pancreatic lobules was monitored simultaneously and signalling responses to various stimuli were directly compared.Ca2+ signals evoked by K+‐induced depolarization were recorded from pancreatic nerve cells. Nerve cell stimulation evoked Ca2+ signals in acinar but not in stellate cells.Stellate cells are not electrically excitable as they, like acinar cells, did not generate Ca2+ signals in response to membrane depolarization.The responsiveness of the stellate cells to bradykinin was markedly reduced in experimental alcohol‐related acute pancreatitis, but they became sensitive to stimulation with trypsin.Our results provide fresh evidence for an important role of stellate cells in acute pancreatitis. They seem to be a critical element in a vicious circle promoting necrotic acinar cell death. Initial trypsin release from a few dying acinar cells generates Ca2+ signals in the stellate cells, which then in turn damage more acinar cells causing further trypsin liberation. AbstractPhysiological Ca2+ signals in pancreatic acinar cells control fluid and enzyme secretion, whereas excessive Ca2+ signals induced by pathological agents induce destructive processes leading to acute pancreatitis. Ca2+ signals in the peri‐acinar stellate cells may also play a role in the development of acute pancreatitis. In this study, we explored Ca2+ signalling in the different cell types in the acinar environment of the pancreatic tissue. We have, for the first time, recorded depolarization‐evoked Ca2+ signals in pancreatic nerves and shown that whereas acinar cells receive a functional cholinergic innervation, there is no evidence for functional innervation of the stellate cells. The stellate, like the acinar, cells are not electrically excitable as they do not generate Ca2+ signals in response to membrane depolarization. The principal agent evoking Ca2+ signals in the stellate cells is bradykinin, but in experimental alcohol‐related acute pancreatitis, these cells become much less responsive to bradykinin and then acquire sensitivity to trypsin. Our new findings have implications for our understanding of the development of acute pancreatitis and we propose a scheme in which Ca2+ signals in stellate cells provide an amplification loop promoting acinar cell death. Initial release of the proteases kallikrein and trypsin from dying acinar cells can, via bradykinin generation and protease‐activated receptors, induce Ca2+ signals in stellate cells which can then, possibly via nitric oxide generation, damage more acinar cells and thereby cause additional release of proteases, generating a vicious circle.

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Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Calcium signalling in the acinar environment of the exocrine pancreas: physiology and pathophysiology

Gryshchenko

Gerasimenko

Peng

et al. 2018

The Journal of Physiology

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“…PSC, quiescent in the healthy pancreas, are located in the basolateral region of acinar cells (462,463). They are characterized by GFAP 1 , desmin, vimentin, nestin, NGF, and NCAM 1 (464).…”

Section: Stroma Dysplasia In Pancreatic Cancermentioning

confidence: 99%

Ping-Pong—Tumor and Host in Pancreatic Cancer Progression

Wang

Zöller

2019

Front. Oncol.

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“…In addition to displaying specific individual functions, the Wnt/β-catenin pathway is known to act cooperatively with other regulatory pathways such as those of TGF-β and NFκβ [23,24]. Both these signalling systems have previously been implicated in pancreatic inflammation, fibrosis and cancer [25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Wnt/β-catenin signalling plays diverse functions during the process of fibrotic remodelling in the exocrine pancreas

et al. 2019

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Background/Objectives: Wnt/β-catenin signalling plays vital roles in tissue homeostasis. Dysregulation of the pathway has been implicated in the pathogenesis of cancer and fibroses in numerous tissues, including the pancreas. We studied the effect of microenvironmental changes pertaining to fibrotic tissue remodelling on the expression of selected Wnt/βcatenin pathway proteins in the human exocrine pancreas. The role of acinar/stellate cross-talk on the expression of the proteins was elucidated in a long-term mouse co-culture system. Methods: Expression of β-catenin, Wnt2, Wnt5a and SFRP4 was analysed immunohistochemically in normal and moderately or highly fibrotic human pancreata (n=8). The effect of humoral interactions on the expression of the proteins was studied by immunocytochemical means in parallel mono-and co-cultures of mouse acinar and stellate cells (PSCs). Results: In human pancreatic tissue, fibrotic microenvironment was associated with redistribution of the proteins in and between epithelial and stromal compartments, compared to acinar-rich tissue. In non-fibrotic and moderately fibrotic tissue the proteins appeared only in acinar cells whereas in highly fibrotic tissue stromal fibroblastoid/stellate cells and macrophages were their predominant locations. Subcellular changes in the expression of β-catenin and Wnt5a were detected. Our in vitro data suggest potential involvement of acinar cell/PSC cross-talk in mediating the changes observed in tissue specimens. Conclusions: Wnt/β-catenin pathway-associated proteins are abundantly expressed in the exocrine pancreas with prominent changes in their cellular and subcellular expression patterns along with increasing levels of fibrosis. Diverse functions for Wnt/ β-catenin signalling during the course of fibrotic remodelling in the exocrine pancreas are suggested.

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Pancreatic stellate cells: what's new?

Abstract: Traditionally, there have been few treatment options for pancreatitis and pancreatic cancer. The elucidation of the wide-ranging functions of PSCs provide an opportunity for treatments based on stromal reprogramming.

Cited by 38 publications

References 60 publications

Calcium signalling in the acinar environment of the exocrine pancreas: physiology and pathophysiology

Calcium signalling in the acinar environment of the exocrine pancreas: physiology and pathophysiology

Ping-Pong—Tumor and Host in Pancreatic Cancer Progression

Wnt/β-catenin signalling plays diverse functions during the process of fibrotic remodelling in the exocrine pancreas

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