The pancreatic stellate cell: a star on the rise in pancreatic diseases

Omary, M. Bishr; Lugea, Aurelia; Lowe, Anson W.; Pandol, Stephen J.

doi:10.1172/jci30082

Cited by 612 publications

(652 citation statements)

References 126 publications

(181 reference statements)

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“…A multitude of factors are important for PSC activation. 2 Among these are factors such as TGF-␤1 and PDGF that are known to be fibrogenic in other organs, such as the liver. 36 The factors that serve as endogenous and negative modulators of fibroblast activation, however, are less well understood.…”

Section: Discussionmentioning

confidence: 99%

“…In response to injury, PSCs become activated, acquire a profibrotic phenotype, degrade the normal matrix, and secrete matrix proteins necessary for scar formation, including fibrillar collagen. 2,3 Similar to hepatic stellate cells, the signals that lead to PSC activation and proliferation have been extensively described. 2 Little is known, however, about the regulators that maintain PSC in a quiescent state.…”

mentioning

confidence: 99%

“…2,3 Similar to hepatic stellate cells, the signals that lead to PSC activation and proliferation have been extensively described. 2 Little is known, however, about the regulators that maintain PSC in a quiescent state.…”

mentioning

confidence: 99%

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Pigment Epithelium-Derived Factor Regulates Early Pancreatic Fibrotic Responses and Suppresses the Profibrotic Cytokine Thrombospondin-1

Schmitz

Protiva

Gattu

et al. 2011

The American Journal of Pathology

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Pigment epithelium-derived factor (PEDF) is important for maintaining the normal extracellular matrix. We hypothesized that the initiation of pancreatic fibrosis is dependent on the loss of PEDF. Pancreatic PEDF expression was assessed in wild-type mice fed either a control or ethanol diet using an intragastric feeding model. Pancreatitis responses were elicited with either a single episode or a repetitive ceruleininduced (50 g/kg, 6 hourly i.p. injections) protocol in wild-type and PEDF-null mice. Quantitative realtime PCR and immunoblotting were performed to assess fibrogenic responses. In wild-type animals, PEDF expression increased with pancreatitis and was more pronounced in mice fed ethanol. Compared with wild-type mice, ␣-smooth muscle actin staining and expression levels of fibrogenic markers (eg, transforming growth factor-␤1, platelet-derived growth factor, collagen I, and thrombospondin-1) were higher in PEDF-null mice at baseline. Sirius red staining revealed more fibrosis in PEDF-null versus wildtype pancreas 1 week after pancreatitis. Differences in tissue fibrosis resolved with longer recovery periods. PEDF overexpression suppressed thrombospondin-1 levels in vitro. Ethanol feeding and experimental pancreatitis increased PEDF expression in wildtype mice. PEDF-null mice, however, demonstrated enhanced early fibrotic responses compared with wildtype mice with pancreatitis. These findings indicate that PEDF acts as a compensatory antifibrotic cytokine in

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Pigment Epithelium-Derived Factor Regulates Early Pancreatic Fibrotic Responses and Suppresses the Profibrotic Cytokine Thrombospondin-1

Schmitz

Protiva

Gattu

et al. 2011

The American Journal of Pathology

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“…During pancreatic injury or inflammation, PSCs are activated by pro-inflammatory cytokines and www.impactjournals.com/oncotarget various growth factors and differentiate into alphasmooth muscle actin (α-SMA)-expressing myofibroblasts [12][13][14][15]. The activated PSCs produce various growth factors, such as platelet-derived growth factor (PDGF), connective tissue growth factor (CTGF) and fibroblast growth factor-2 (FGF2) which in turn induce tumor cell proliferation, invasion, angiogenesis, and metastasis as well as confer development of resistance to chemotherapy [16][17][18][19][20][21][22][23]. Blockade of PSC activation might, therefore, be an interesting approach to inhibit their tumor-inducing actions.…”

Section: Introductionmentioning

confidence: 99%

150 MicroRNA-199a and 214 as potential therapeutic targets in pancreatic stellate cells in pancreatic tumor

Kuninty¹,

Bojmar²,

Sandström³

et al. 2015

European Journal of Cancer

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“…[1][2][3][4][5] PSCs are localized to the periacinar, perivascular, and periductal regions of the pancreas, 3,4,[6][7][8][9] and have an important role in the pathobiology of chronic pancreatitis (CP) and pancreatic cancer. [1][2][3][4][5] In these clinical settings, PSCs take part in disease pathogenesis following transformation from a quiescent state into an activated or 'myofibroblastic' state. [1][2][3][4][5] PSCs are controlled by autocrine and paracrine stimuli and have similarities to hepatic stellate cells.…”

mentioning

confidence: 99%

Transforming growth factor-α activates pancreatic stellate cells and may be involved in matrix metalloproteinase-1 upregulation

Tahara

Sato

Yamazaki

et al. 2013

Laboratory Investigation

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The role that transforming growth factor-a (TGF-a) has in chronic pancreatitis and pancreatic cancer has not been fully elucidated. We evaluated the effects of TGF-a on the human pancreatic stellate cell (PSC) line RLT-PSC and primary human PSCs, and the expression levels of TGF-a and metalloproteinase-1 (MMP-1) in human chronic pancreatitis and pancreatic cancer tissues. TGF-a stimulated the proliferation and migration of PSCs. Although the mRNA expression levels of tissue inhibitor of metalloproteinase-1 and a1(I) collagen were unchanged, the mRNA expression levels of MMP-1 increased concomitant with increases in MMP-1 protein levels and collagenase activity. TGF-a-stimulated migration of RLT-PSC cells was partially blocked by tissue inhibitor of metalloproteinase-1 protein and MMP-1 small interfering RNA. MMP-1 was also observed to stimulate the migration of PSCs. TGF-a-induced MMP-1 expression was completely blocked by gefitinib in PSCs. The Ras-ERK and PI3/Akt pathways appear to be involved in the activation of MMP-1 in PSCs. Immunohistochemical analyses showed that MMP-1 expression was significantly increased in the pancreatic interstitial tissues in case of chronic pancreatitis or pancreatic cancer compared with those in case of normal pancreas. In conclusion, TGF-a increased proliferation and migration of PSCs. TGF-a-induced migration of cells may be partly due to upregulation of MMP-1. TGF-a and MMP-1 upregulation may contribute to the pathogenesis of chronic pancreatitis and pancreatic cancer.

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The pancreatic stellate cell: a star on the rise in pancreatic diseases

Cited by 612 publications

References 126 publications

Pigment Epithelium-Derived Factor Regulates Early Pancreatic Fibrotic Responses and Suppresses the Profibrotic Cytokine Thrombospondin-1

Pigment Epithelium-Derived Factor Regulates Early Pancreatic Fibrotic Responses and Suppresses the Profibrotic Cytokine Thrombospondin-1

150 MicroRNA-199a and 214 as potential therapeutic targets in pancreatic stellate cells in pancreatic tumor

Transforming growth factor-α activates pancreatic stellate cells and may be involved in matrix metalloproteinase-1 upregulation

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