Rat Pancreatic Stellate Cells Research Articles

Green tea polyphenol epigallocatechin-3-gallate blocks PDGF-induced proliferation and migration of rat pancreatic stellate cells

To clarify the effects of epigallocatechin-3-gallate (EGCG) on the platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of pancreatic stellate cells (PSCs). PSCs were isolated from rat pancreas tissue and used in their culture-activated, myofibroblast-like phenotype. Cell proliferation was assessed by measuring the incorporation of 5-bromo-2'-deoxyuridine. Cell migration was assessed using modified Boyden chambers. Cyclin D1, p21Waf1, and p27Kip1 expression and phosphorylation of PDGF beta-receptor, extracellular signal-regulated kinase, and Akt were examined by Western blotting. Activation of phospha-tidylinositol 3-kinase was examined by kinase assay using phosphatidylinositol as a substrate. Cell cycle was assessed by flow cytometry after staining with propidium iodide. EGCG at non-cytotoxic concentrations inhibited PDGF-induced proliferation and migration. This effect was associated with the inhibition of cell cycle progression beyond the G1 phase, decreased cyclin D1 and increased p27Kip1 expression. EGCG inhibited tyrosine phosphorylation of PDGF beta-receptor and downstream activation of extracellular signal-regulated kinase and phosphatidylinositol 3-kinase/Akt pathways. EGCG inhibited PDGF-BB-induced proliferation and migration of PSCs through the inhibition of PDGF-mediated signaling pathways.

Desmoplastic reaction in pancreatic cancer: role of pancreatic stellate cells.

Pancreatic cancer has a very poor prognosis, largely due to its propensity for early local and distant spread. Histopathologically, most pancreatic cancers are characterized by a prominent stromal/fibrous reaction in and around tumor tissue. The aims of this study were to determine whether (1) the cells responsible for the formation of the stromal reaction in human pancreatic cancers are activated pancreatic stellate cells (PSCs) and (2) an interaction exists between pancreatic cancer cells and PSCs that may facilitate local and distant invasion of tumor. Serial sections of human pancreatic cancer tissue were stained for desmin and glial fibrillary acidic protein (stellate cell selective markers) and alpha-smooth muscle actin (alphaSMA), a marker of activated PSC activation, by immunohistochemistry, and for collagen using Sirius Red. Correlation between the extent of positive staining for collagen and alphaSMA was assessed by morphometry. The cellular source of collagen in stromal areas was identified using dual staining methodology, ie, immunostaining for alphaSMA and in situ hybridization for procollagen alpha1I mRNA. The possible interaction between pancreatic cancer cells and PSCs was assessed in vitro by exposing cultured rat PSCs to control medium or conditioned medium from 2 pancreatic cancer cell lines (PANC-1 and MiaPaCa-2) for 24 hours. PSC activation was assessed by cell proliferation and alphaSMA expression. Stromal areas of human pancreatic cancer stained strongly positive for the stellate cell selective markers desmin and GFAP (indicating the presence of PSCs), for alphaSMA (suggesting that the PSCs were in their activated state) and for collagen. Morphometric analysis demonstrated a close correlation (r = 0.77; P < 0.04; 8 paired sections) between the extent of PSC activation and collagen deposition. Procollagen mRNA expression was localized to alphaSMA-positive cells in stromal areas indicating that activated PSCs were the predominant source of collagen in stromal areas. Exposure of PSCs to pancreatic cancer cell secretions in vitro resulted in PSC activation as indicated by significantly increased cell proliferation and alphaSMA expression. Activated PSCs are present in the stromal reaction in pancreatic cancers and are responsible for the production of stromal collagen. PSC function is influenced by pancreatic cancer cells. Interactions between tumor cells and stromal cells (PSCs) may play an important role in the pathobiology of pancreatic cancer.

Pancreatic cancer stimulates pancreatic stellate cell proliferation and TIMP-1 production through the MAP kinase pathway

Pancreatic adenocarcinoma is characterized by an intense desmoplastic reaction that surrounds the tumor. Pancreatic stellate cells (PSCs) are thought to be responsible for production of this extracellular matrix. When activated, PSCs have a myofibroblast phenotype and produce not only components of the extracellular matrix including collagen, fibronectin, and laminin, but also matrix metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs). Since PSCs are found in the stroma surrounding human pancreatic adenocarcinoma, we postulate that pancreatic cancer could impact PSC proliferation and TIMP-1 production. Rat PSCs were isolated and cultured. Isolated PSCs were exposed to PANC-1 conditioned medium (CM) and proliferation, activation of the mitogen-activated protein (MAP) kinase pathway, and TIMP-1 gene induction were determined. Exposure to PANC-1 CM increased PSC DNA synthesis, cell number, and TIMP-1 mRNA (real-time PCR) as well as activating the extracellular-regulated kinase (ERK) 1/2. Inhibition of ERK 1/2 phosphorylation (U0126) prevented the increases in growth and TIMP-1 expression. PANC-1 CM stimulates PSC proliferation and TIMP-1 through the MAP kinase (ERK 1/2) pathway.

Protease-activated receptor-2-mediated proliferation and collagen production of rat pancreatic stellate cells.

Activated pancreatic stellate cells (PSCs) play a pivotal role in the pathogenesis of pancreatic inflammation and fibrosis. Trypsin and tryptase, which are agonists for protease-activated receptor-2 (PAR-2), are involved in the pathogenesis of pancreatitis. Here, we examined whether PSCs expressed PAR-2 and its agonists affect the cell functions of PSCs. PSCs were isolated from rat pancreas tissue. Expression of PAR-2 was examined by Western blotting and reverse transcription-polymerase chain reaction. Trypsin, activating peptide (SLIGRL-NH(2), corresponding to the PAR-2 tethered ligand), and tryptase were tested for their ability to affect proliferation, chemokine production, and collagen synthesis in culture-activated PSCs. Activation of mitogen-activated protein (MAP) kinases was assessed by Western blotting using antiphosphospecific antibodies. The effect of PAR-2 agonists on the activation of freshly isolated PSCs in culture was also examined. PAR-2 expression was observed in culture-activated PSCs, whereas it was undetectable in freshly isolated PSCs. PAR-2 agonists activated activator protein-1 and MAP kinases (extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 MAP kinase) but not nuclear factor kappaB. PAR-2 agonists induced proliferation of PSCs through the activation of extracellular signal-regulated kinase. PAR-2 agonists increased collagen synthesis through the activation of c-Jun N-terminal kinase and p38 MAP kinase. PAR-2 agonists did not induce the production of monocyte chemoattractant protein-1 and cytokine-induced neutrophil chemoattractant-1 or initiate the transformation of freshly isolated PSCs in culture. Taken together, our results suggest a role of PAR-2 in the sustenance of pancreatic fibrosis through the increased proliferation and collagen production in PSCs.

Pressure activates rat pancreatic stellate cells.

Pancreatic stellate cells (PSCs) play a central role in development of pancreatic fibrosis. In chronic pancreatitis, pancreatic tissue pressure is higher than that of the normal pancreas. We here evaluate the effects of pressure on the activation of rat PSCs. PSCs were isolated from the pancreas of Wistar rat using collagenase digestion and centrifugation with Nycodenz gradient. Pressure was applied to cultured rat PSCs by adding compressed helium gas into the pressure-loading apparatus to raise the internal pressure. Cell proliferation rate was assessed by 5-bromo-2'-deoxyuridine (BrdU) incorporation. MAPK protein levels and alpha-smooth muscle actin (alpha-SMA) expression were evaluated by Western blot analysis. Concentration of activated transforming growth factor-beta1 (TGF-beta1) secreted from PSCs into culture medium was determined by ELISA. Collagen type I mRNA expression and collagen secretion were assessed by quantitative PCR and Sirius red dye binding assay, respectively. Application of pressure significantly increased BrdU incorporation and alpha-SMA expression. In addition, pressure rapidly increased the phosphorylation of p44/42 and p38 MAPK. Treatment of PSCs with an MEK inhibitor and p38 MAPK inhibitor suppressed pressure-induced cell proliferation and alpha-SMA expression, respectively. Moreover, pressure significantly promoted activated TGF-beta1 secretion, collagen type I mRNA expression, and collagen secretion. Our results demonstrate that pressure itself activates rat PSCs and suggest that increased pancreatic tissue pressure may accelerate the development of pancreatic fibrosis in chronic pancreatitis.

Troglitazone inhibits the progression of chronic pancreatitis and the profibrogenic activity of pancreatic stellate cells via a PPARgamma-independent mechanism.

We have previously reported that troglitazone inhibits proinflammatory cytokine production in chronic pancreatitis. In the present study, we show that troglitazone prevents the progression of chronic pancreatitis by inhibiting the proliferation of pancreatic stellate cells (PSCs) via a PPARgamma-independent mechanism. WBN/Kob rats with spontaneous chronic pancreatitis were fed troglitazone-containing rat chow for 3 or 6 months. Pancreatic fibrosis and expression of alpha-SMA were markedly attenuated by troglitazone. Rat PSCs expressed a higher level of PPARgamma1 mRNA than of PPARgamma2 mRNA. PSCs were transiently cotransfected with a dominant negative mutant PPARgamma1 and a PPAR-driven reporter gene. Troglitazone increased reporter activity and the mutant receptor abrogated wild-type receptor activity in a dose-dependent manner. Troglitazone inhibited cell proliferation by blocking cell-cycle progression beyond the G1 phase. These effects were observed in mutant receptor-transfected cells as well as cells transfected with the control vector. The effect of troglitazone on alpha1(I) procollagen mRNA and MCP-1 mRNA was unaffected by inhibition of endogenous PPARgamma1 receptor activity. These results suggest that troglitazone may serve as novel therapeutic agent for the treatment of chronic pancreatitis. The antifibrotic effect of troglitazone appears to be mediated, in part, via a PPARgamma-independent mechanism.

Effects of Angiotensin II on Rat Pancreatic Stellate Cells

The aim of the study was to identify pancreatic stellate cells (PSCs) as a potential target of angiotensin II (ATII) action because recently a local renin-angiotensin system (RAS) has been described in the pancreas. PSCs were isolated from male Wistar rats and investigated for ATII receptor expression and ATII-induced calcium transients, contractions, proliferation, and alpha-smooth muscle actin expression. Quiescent and activated PSCs expressed the ATII receptor subtype AT1 but not AT2. Addition of ATII led to a rapid elevation of intracellular calcium ([Ca]i). The sensitivity toward ATII with respect to calcium transients did not change during the transdifferentiation process. In activated PSCs, ATII dose dependently induced PSC cell contraction. Furthermore, ATII induced an activation of the c-Jun-N-terminal kinase (JNK) and extracellular regulated kinase (Erk), which was inhibited after intracellular calcium chelation by BAPTA-AM. The p38 mitogen-activated protein kinase (p38) was also activated by ATII. BAPTA-AM itself induced p38 activation, which was not further enhanced by ATII. ATII stimulated PSC proliferation, while PSC transdifferentiation, as indicated by alpha-smooth muscle actin expression and collagen type I secretion, was not enhanced. The data suggest that PSCs are targets of ATII action with potential pathophysiological relevance.

Generation and characterization of immortalized rat pancreatic stellate cells.

Pancreatic stellate cells (PSCs) are involved in, among other things, the pathogenesis of pancreatic fibrosis. Here, we present the generation of immortalized PSCs 7 and 14 days after isolation by retroviral gene transfer of the SV40 large T antigen encoding region. Propagated cell lines [large T immortalized cells (LTC)-7, LTC-14] retained characteristics of primary cells in terms of morphology, responsiveness to mediators regulating cellular functions such as proliferation, and expression profile of a number of investigated genes. Whereas LTC-14 kept the morphological features of the differentiation status of the primary cells they were made of, LTC-7 appeared similar to an earlier stage. Thus the established cell lines represent a versatile tool to investigate various aspects of PSC biology.

Angiotensin II stimulates DNA synthesis of rat pancreatic stellate cells by activating ERK through EGF receptor transactivation

Although angiotensin II (Ang II) is known to participate in pancreatic fibrosis, little is known as to the mechanism by which Ang II promotes pancreatic fibrosis. To elucidate the mechanism, we examined the action of Ang II on the proliferation of rat pancreatic stellate cells (PSCs) that play central roles in pancreatic fibrosis. Immunocytochemistry and Western blotting demonstrated that both Ang II type 1 and type 2 receptors were expressed in PSCs. [ 3H]Thymidine incorporation assay revealed that Ang II enhanced DNA synthesis in PSCs, which was blocked by Ang II type 1 receptor antagonist losartan. Western blotting using anti-phospho-epidermal growth factor (EGF) receptor and anti-phospho-extracellular signal regulated kinase (ERK) antibodies showed that Ang II-activated EGF receptor and ERK. Both EGF receptor kinase inhibitor AG1478 and MEK1 inhibitor PD98059 attenuated ERK activation and DNA synthesis enhanced by Ang II. These results indicate that Ang II stimulates PSC proliferation through EGF receptor transactivation—ERK activation pathway.

Involvement of AP-1 proteins in pancreatic stellate cell activation in vitro.

Pancreatic stellate cells (PSCs) play a key role in the development of pancreatic fibrosis. The molecular mechanisms underlying their activation in response to profibrogenic mediators, however, are largely unknown. Extending previous studies on the transcriptional regulation of PSC activation, we have now focused on the involvement of activator protein (AP)-1. Using cultured rat PSCs, phenotypic transition of PSCs towards activated myofibroblasts was monitored by an immunoblot analysis of alpha-smooth muscle actin (alpha-SMA) expression. Transcription factor activation profiles were studied by electrophoretic mobility shift assays. DNA synthesis in PSCs was assessed through the quantification of 5-bromo-2'-deoxyuridine incorporation. Activated AP-1 complexes were detectable already before high levels of alpha-SMA were expressed. Maximal DNA binding activity of AP-1, as well as of NF-kappaB, was observed early in the course of PSC culture, while the strongest activation of STAT3 was observed much later. A detailed analysis of AP-1 complex composition revealed that phenotypic transition of PSCs towards myofibroblasts was accompanied by an increase of the JunD content relative to the one of JunB. Studies on the role of JunB and JunD in PSC activation indicated an inhibition of platelet-derived growth factor-induced DNA synthesis by antisense oligonucleotides to JunB but not JunD. The results of this study implicate AP-1 in PSC activation and suggest distinct roles of individual Jun proteins in the regulation of PSC function. In further studies, it should be analyzed whether signaling pathways involved in PSC activation might be suitable targets for antifibrotic therapies.

Pancreatic stellate cell migration: role of the phosphatidylinositol 3-kinase (PI3-kinase) pathway

Pancreatic stellate cells (PSCs) are implicated as key mediators of pancreatic fibrogenesis and are found in increased numbers in areas of pancreatic injury. This increase in number may be due to increased local proliferation and/or migration of PSCs to affected areas from surrounding tissue. We have recently shown that PSCs can migrate and that this migration is stimulated by PDGF in a predominantly chemotactic manner [Gut 52 (2003) 677]. However, the signalling mechanisms responsible for PDGF-induced PSC migration are not known. Aims: (i) To determine whether PDGF-induced PSC migration is mediated by the PI3-kinase pathway. (ii) To investigate whether cell migration is influenced by cell proliferation and whether an interaction exists between the PI3-kinase pathway and the ERK1/2 pathway (known to mediate cell proliferation) in PSCs exposed to PDGF. Methods: (i) PI3-kinase activity was assessed by measuring the activation (phosphorylation) of its downstream substrate Akt in rat PSCs incubated with PDGF (10 ng/mL) for 5 min, 15 min, 60 min, and 24 hr in the presence or absence of the specific PI3-kinase inhibitor wortmannin. (ii) The role of the PI3-kinase pathway in PSC migration was examined by assessing PSC migration through a porous membrane after exposure to PDGF in the presence and absence of wortmannin for 24 hr. (iii) The relationship between migration and proliferation was assessed by examining migration of PSCs exposed to PDGF in the presence and absence of mitomycin C, an inhibitor of cell proliferation. (iv) The interaction between PI3-kinase and ERK1/2 was examined by incubation of PSCs with PDGF in the presence and absence of wortmannin, followed by assessment of ERK1/2 activation by western blot. Results: PDGF increased Akt activation in PSCs as early as at 5 min of incubation and this increase was sustained for 24 hr. Inhibition of PI3-kinase by wortmannin decreased basal as well as PDGF-induced migration and also inhibited ERK1/2 activation. Inhibition of PSC proliferation with mitomycin C significantly reduced (but did not abolish) basal and PDGF-induced PSC migration. Conclusions: (i) The PI3-kinase pathway is induced in PSCs after exposure to PDGF and this induction is sustained for at least 24 hr. (ii) The PI3-kinase pathway plays a role in PDGF-induced PSC migration and is partially involved in mediating ERK1/2 activation. (iii) PSC migration is dependent, at least in part, on cell proliferation.

4-hydroxy-2, 3-nonenal activates activator protein-1 and mitogen-activated protein kinases in rat pancreatic stellate cells.

Activated pancreatic stellate cells (PSCs) are implicated in the pathogenesis of pancreatic inflammation and fibrosis, where oxidative stress is thought to play a key role. 4-hydroxy-2,3-nonenal (HNE) is generated endogenously during the process of lipid peroxidation, and has been accepted as a mediator of oxidative stress. The aim of this study was to clarify the effects of HNE on the activation of signal transduction pathways and cellular functions in PSCs. PSCs were isolated from the pancreas of male Wistar rats after perfusion with collagenase P, and used in their culture-activated, myofibroblast-like phenotype unless otherwise stated. PSCs were treated with physiologically relevant and non-cytotoxic concentrations (up to 5 micromol/L) of HNE. Activation of transcription factors was examined by electrophoretic mobility shift assay and luciferase assay. Activation of mitogen-activated protein (MAP) kinases was assessed by Western blotting using anti-phosphospecific antibodies. Cell proliferation was assessed by measuring the incorporation of 5-bromo-2'-deoxyuridine. Production of type I collagen and monocyte chemoattractant protein-1 was determined by enzyme-linked immunosorbent assay. The effect of HNE on the transformation of freshly isolated PSCs in culture was also assessed. HNE activated activator protein-1, but not nuclear factor kappaB. In addition, HNE activated three classes of MAP kinases: extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 MAP kinase. HNE increased type I collagen production through the activation of p38 MAP kinase and c-Jun N-terminal kinase. HNE did not alter the proliferation, or monocyte chemoattractant protein-1 production. HNE did not initiate the transformation of freshly isolated PSCs to myofibroblast-like phenotype. Specific activation of these signal transduction pathways and altered cell functions such as collagen production by HNE may play a role in the pathogenesis of pancreatic disorders.

Pancreatic stellate cell activation by ethanol and acetaldehyde: is it mediated by the mitogen-activated protein kinase signaling pathway?

Pancreatic fibrosis is a characteristic feature of alcoholic chronic pancreatitis. Recent studies suggest that activated pancreatic stellate cells (PSCs) are the major cell-type involved in pancreatic fibrogenesis. Cultured PSCs become activated when exposed to ethanol or its metabolite acetaldehyde (as indicated by increased alpha-smooth muscle actin [alpha-SMA] expression and increased collagen synthesis). However the intracellular signaling mechanisms responsible for ethanol- or acetaldehyde-induced PSC activation remain to be fully elucidated. One of the major signaling pathways known to regulate protein synthesis in mammalian cells is the mitogen-activated protein kinase (MARK) pathway. To examine the effects of ethanol and acetaldehyde on the MAPK pathway (by assessing the activities of the 3 major subfamilies (extracellular-regulated kinases 1 and 2 [ERK 1/2], JNK and p38 kinase) in PSCs and to examine the role of p38 kinase in mediating the ethanol- and acetaldehyde-induced increase in alpha-SMA expression in activated rat PSCs. Rat PSCs were incubated with ethanol (50 mM) or acetaldehyde (200 microM) for 15 min, 30 min, 60 min, and 24 h; and activities of ERK 1/2, JNK, and p38 kinase were assessed in cell lysates using kinase assays and Western blot. In addition, rat PSCs were treated with the specific p38 MAPK inhibitor SB203580 in the presence or absence of ethanol or acetaldehyde for 24h, and activation of the downstream protein kinase MAPKAP kinase-2 (an indicator of p38 MAPK activity) was assessed by Western blot. Specific inhibitors were also used to inhibit the activity of ERK 1/2 and JNK. Following inhibition of the above signaling pathways, alpha-SMA expression by PSCs was assessed by Western blot. Ethanol and acetaldehyde increased the activation of all 3 subfamilies (ERK 1/2, JNK and p38 kinase) of the MAPK pathway in PSCs. Treatment of PSCs with SB203580 abolished the ethanol- and acetaldehyde-induced increase in p38 MAPK activity and also prevented the induction of alpha-SMA expression in PSCs. However, inhibition of ERK 1/2 and JNK had no effect on ethanoland acetaldehyde-induced alpha-SMA expression in PSCs. (1) The MAP kinase pathway is induced in PSCs after exposure to ethanol or acetaldehyde and this induction is sustained for at least 24h. (2) The p38 MAPK pathway mediates the activation (as indicated by increased alpha-SMA expression) of PSCs by ethanol or acetaldehyde.

Regulation of pancreatic stellate cell function in vitro: biological and molecular effects of all-trans retinoic acid

Pancreatic stellate cells (PSCs) are essentially involved in the development of pancreatic fibrosis, a constant feature of chronic pancreatitis and pancreatic cancer. Profibrogenic mediators, such as ethanol metabolites and cytokines, induce a PSC activation process that involves proliferation, enhanced production of extracellular matrix proteins and a phenotypic transition towards myofibroblasts which includes a loss of the characteristic retinoid-containing fat droplets. Here, we have analysed how exogenous all-trans retinoic acid (ATRA) affects activation of rat PSCs induced by sustained culture. Bromodeoxyuridine-incorporation assays indicated an ATRA-dependent inhibition of DNA synthesis. In contrast, ATRA did not affect expression of α-smooth muscle actin, a protein typical for myofibroblasts. Quantification of [3H]proline incorporation revealed a diminished collagen production in ATRA-treated PSCs. Furthermore, zymography experiments showed that supernatants of ATRA-exposed PSC cultures contained higher levels of matrix metalloproteinase-9 but not of matrix metalloproteinase-2 than untreated controls. At the level of intracellular signalling, ATRA had no effect on extracellular signal-regulated kinase activation after incubation of PSCs with the mitogen platelet-derived growth factor (PDGF). In addition, PDGF-induced DNA binding of activator protein-1 (AP-1) transcription factors was not inhibited by ATRA treatment. Luciferase reporter gene assays, however, revealed an ATRA-dependent transrepression of AP-1 in PDGF-stimulated PSCs. Together, the results indicate that exogenous ATRA displays inhibitory effects on PSC proliferation and collagen synthesis but does not block phenotypic transition towards myofibroblasts. We hypothesise that inhibition of AP-1 signalling may be involved in the mediation of biological effects of ATRA on PSCs.

Production and effects of endothelin-1 in rat pancreatic stellate cells.

Proliferation and matrix synthesis of activated pancreatic stellate cells (PSCs) participate in the development of chronic pancreatitis. Besides other substances, endothelin-1 (ET-1) may influence the activation process of PSCs. Until now, ET-1 has not been studied in this particular cell type. To characterize PSCs in rat pancreas with respect to expression of ET(A)-receptors, production of ET-1, and physiological effects induced by ET-1 during PSC activation. Immunocytochemical and ELISA techniques and cDNA microarray analysis were used. Physiologic effects were characterized by single cell measurements of free cytosolic Ca2+-concentration and of PSC contractility on collagen lattices. Activation of PSCs in vitro, as assessed by alpha-smooth muscle actin expression, was accompanied by the de novo expression of ET(A)-receptors and synthesis of ET-1 mRNA and protein. Cytosolic Ca2+-concentration was increased upon ET-1 stimulation in activated but not in quiescent PSCs. Contractility of activated PSCs was significantly reduced by the selective ET(A)-receptor antagonist BQ123 but not by the ET(B)-receptor antagonist IRL-1038. The results suggest that ET-1 may act as a paracrine and autocrine factor for activated PSCs and may mediate contractions of activated, but not quiescent, PSCs.

Anti-fibrogenic effects of thiazolidine derivatives are mediated via PPARγ1-dependent and independent mechanism in rat pancreatic stellate cells

Anti-fibrogenic effects of thiazolidine derivatives are mediated via PPARγ1-dependent and independent mechanism in rat pancreatic stellate cells

Oxidative stress activates activator protein-1 and mitogen-activated protein kinases in rat pancreatic stellate cells

Oxidative stress activates activator protein-1 and mitogen-activated protein kinases in rat pancreatic stellate cells

Pressure induced rat pancreatic stellate cells proliferate through activation of mitogen-activated protein kinase

Pressure induced rat pancreatic stellate cells proliferate through activation of mitogen-activated protein kinase

Role of Rho/Rho kinases pathway in the activation of rat pancreatic stellate cells

Role of Rho/Rho kinases pathway in the activation of rat pancreatic stellate cells

Differential roles of signal transduction pathways for platelet-derived growth factor-induced proliferation and migration of rat pancreatic stellate cells

Differential roles of signal transduction pathways for platelet-derived growth factor-induced proliferation and migration of rat pancreatic stellate cells