| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
From the Departments of Gastroenterology*
and
Surgery,
Pancreatic Research Group, Prince of
Wales Hospital, University of New South Wales, Sydney; and the
Department of Medicine,
Hepatic Fibrosis
Group, Clinical Sciences Unit, Queensland, Institute of Medical
Research and the University of Queensland Brisbane, Australia
The mechanisms of pancreatic fibrosis are poorly understood. In the
liver, stellate cells play an important role in fibrogenesis.
Similar cells have recently been isolated from the pancreas and are
termed pancreatic stellate cells. The aim of this study was to
determine whether pancreatic stellate cell activation occurs during
experimental and human pancreatic fibrosis. Pancreatic fibrosis was
induced in rats (n = 24) by infusion of
trinitrobenzene sulfonic acid (TNBS) into the pancreatic duct. Surgical
specimens were obtained from patients with chronic pancreatitis
(n = 6). Pancreatic fibrosis was assessed using the
Sirius Red stain and immunohistochemistry for collagen type I.
Pancreatic stellate cell activation was assessed by staining for
-smooth muscle actin (SMA), desmin, and
platelet-derived growth factor receptor type ß (PDGFRß). The
relationship of fibrosis to stellate cell activation was studied by
staining of serial sections for SMA, desmin,
PDGFRß, and collagen, and by dual-staining for SMA
plus either Sirius Red or in situ hybridization for
procollagen 1 (I) mRNA. The cellular source of TGFß
was examined by immunohistochemistry. The histological appearances in
the TNBS model resembled those found in human chronic pancreatitis.
Areas of pancreatic fibrosis stained positively for Sirius Red and
collagen type I. Sirius Red staining was associated with
SMA-positive cells. SMA staining colocalized with
procollagen 1 (I) mRNA expression. In the rat
model, desmin staining was associated with PDGFRß in areas of
fibrosis. TGFß was maximal in acinar cells adjacent to areas of
fibrosis and spindle cells within fibrotic bands. Pancreatic stellate
cell activation is associated with fibrosis in both human pancreas and
in an animal model. These cells appear to play an important role in
pancreatic fibrogenesis.
This article has been cited by other articles:
 |
|
 |
|
  J. Webber, S. Meran, R. Steadman, and A. Phillips Hyaluronan Orchestrates Transforming Growth Factor-{beta}1-dependent Maintenance of Myofibroblast Phenotype J. Biol. Chem., April 3, 2009; 284(14): 9083 - 9092. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Vonlaufen, S. Joshi, C. Qu, P. A. Phillips, Z. Xu, N. R. Parker, C. S. Toi, R. C. Pirola, J. S. Wilson, D. Goldstein, et al. Pancreatic Stellate Cells: Partners in Crime with Pancreatic Cancer Cells Cancer Res., April 1, 2008; 68(7): 2085 - 2093. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Masamune, T. Watanabe, K. Kikuta, K. Satoh, and T. Shimosegawa NADPH oxidase plays a crucial role in the activation of pancreatic stellate cells Am J Physiol Gastrointest Liver Physiol, January 1, 2008; 294(1): G99 - G108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Mahadevan and D. D. Von Hoff Tumor-stroma interactions in pancreatic ductal adenocarcinoma Mol. Cancer Ther., April 1, 2007; 6(4): 1186 - 1197. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. R. Jerrells, D. Vidlak, and J. M. Strachota Alcoholic pancreatitis: mechanisms of viral infections as cofactors in the development of acute and chronic pancreatitis and fibrosis J. Leukoc. Biol., February 1, 2007; 81(2): 430 - 439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Schneiderhan, F. Diaz, M. Fundel, S. Zhou, M. Siech, C. Hasel, P. Moller, J. E. Gschwend, T. Seufferlein, T. Gress, et al. Pancreatic stellate cells are an important source of MMP-2 in human pancreatic cancer and accelerate tumor progression in a murine xenograft model and CAM assay J. Cell Sci., February 1, 2007; 120(3): 512 - 519. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Aoki, H. Ohnishi, K. Hama, S. Shinozaki, H. Kita, H. Osawa, H. Yamamoto, K. Sato, K. Tamada, and K. Sugano Cyclooxygenase-2 is required for activated pancreatic stellate cells to respond to proinflammatory cytokines Am J Physiol Cell Physiol, January 1, 2007; 292(1): C259 - C268. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Laplante, M.-A. Raymond, A. Labelle, J.-I. Abe, R. V. Iozzo, and M.-J. Hebert Perlecan Proteolysis Induces an {alpha}2beta1 Integrin- and Src Family Kinase-dependent Anti-apoptotic Pathway in Fibroblasts in the Absence of Focal Adhesion Kinase Activation J. Biol. Chem., October 13, 2006; 281(41): 30383 - 30392. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T Reding, D Bimmler, A Perren, L-K Sun, F Fortunato, F Storni, and R Graf A selective COX-2 inhibitor suppresses chronic pancreatitis in an animal model (WBN/Kob rats): significant reduction of macrophage infiltration and fibrosis Gut, August 1, 2006; 55(8): 1165 - 1173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. G. Docherty, O. E. O'Sullivan, D. A. Healy, M. Murphy, A. J. O'Neill, J. M. Fitzpatrick, and R. W. G. Watson TGF-beta1-induced EMT can occur independently of its proapoptotic effects and is aided by EGF receptor activation Am J Physiol Renal Physiol, May 1, 2006; 290(5): F1202 - F1212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Masamune, M. Satoh, J. Hirabayashi, K. Kasai, K. Satoh, and T. Shimosegawa Galectin-1 induces chemokine production and proliferation in pancreatic stellate cells Am J Physiol Gastrointest Liver Physiol, April 1, 2006; 290(4): G729 - G736. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Aoki, H. Ohnishi, K. Hama, T. Ishijima, Y. Satoh, K. Hanatsuka, A. Ohashi, S. Wada, T. Miyata, H. Kita, et al. Autocrine loop between TGF-beta1 and IL-1beta through Smad3- and ERK-dependent pathways in rat pancreatic stellate cells Am J Physiol Cell Physiol, April 1, 2006; 290(4): C1100 - C1108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Sparmann, A. Glass, P. Brock, R. Jaster, D. Koczan, H.-J. Thiesen, S. Liebe, and J. Emmrich Inhibition of lymphocyte apoptosis by pancreatic stellate cells: impact of interleukin-15 Am J Physiol Gastrointest Liver Physiol, November 1, 2005; 289(5): G842 - G851. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S J Pandol Are we studying the correct state of the stellate cell to elucidate mechanisms of chronic pancreatitis? Gut, June 1, 2005; 54(6): 744 - 745. [Full Text] [PDF]
|
|
|
|
|
|
F Manapov, P Muller, and J Rychly Translocation of p21Cip1/WAF1 from the nucleus to the cytoplasm correlates with pancreatic myofibroblast to fibroblast cell conversion Gut, June 1, 2005; 54(6): 814 - 822. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Yamada, A. Kuno, K. Ogawa, M. Tang, K. Masuda, S. Nakamura, T. Ando, T. Okamoto, H. Ohara, T. Nomura, et al. Combination Therapy with an Angiotensin-Converting Enzyme Inhibitor and an Angiotensin II Receptor Blocker Synergistically Suppresses Chronic Pancreatitis in Rats J. Pharmacol. Exp. Ther., April 1, 2005; 313(1): 36 - 45. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. van Westerloo, S. Florquin, A. M. de Boer, J. Daalhuisen, A. F. de Vos, M. J. Bruno, and T. van der Poll Therapeutic Effects of Troglitazone in Experimental Chronic Pancreatitis in Mice Am. J. Pathol., March 1, 2005; 166(3): 721 - 728. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Masamune, K. Kikuta, M. Satoh, N. Suzuki, and T. Shimosegawa Protease-Activated Receptor-2-Mediated Proliferation and Collagen Production of Rat Pancreatic Stellate Cells J. Pharmacol. Exp. Ther., February 1, 2005; 312(2): 651 - 658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Vittal, J. C. Horowitz, B. B. Moore, H. Zhang, F. J. Martinez, G. B. Toews, T. J. Standiford, and V. J. Thannickal Modulation of Prosurvival Signaling in Fibroblasts by a Protein Kinase Inhibitor Protects against Fibrotic Tissue Injury Am. J. Pathol., February 1, 2005; 166(2): 367 - 375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Watanabe, Y. Nagashio, H. Asaumi, Y. Nomiyama, M. Taguchi, M. Tashiro, Y. Kihara, H. Nakamura, and M. Otsuki Pressure activates rat pancreatic stellate cells Am J Physiol Gastrointest Liver Physiol, December 1, 2004; 287(6): G1175 - G1181. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Armstrong, G. Packham, L. B. Murphy, A. C. Bateman, J. A. Conti, D. R. Fine, C. D. Johnson, R. C. Benyon, and J. P. Iredale Type I Collagen Promotes the Malignant Phenotype of Pancreatic Ductal Adenocarcinoma Clin. Cancer Res., November 1, 2004; 10(21): 7427 - 7437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Masamune, K. Kikuta, N. Suzuki, M. Satoh, K. Satoh, and T. Shimosegawa A c-Jun NH2-Terminal Kinase Inhibitor SP600125 (Anthra[1,9-cd]pyrazole-6 (2H)-one) Blocks Activation of Pancreatic Stellate Cells J. Pharmacol. Exp. Ther., August 1, 2004; 310(2): 520 - 527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Nagashio, H. Asaumi, S. Watanabe, Y. Nomiyama, M. Taguchi, M. Tashiro, T. Sugaya, and M. Otsuki Angiotensin II type 1 receptor interaction is an important regulator for the development of pancreatic fibrosis in mice Am J Physiol Gastrointest Liver Physiol, July 1, 2004; 287(1): G170 - G177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Sparmann, C. Hohenadl, J. Tornoe, R. Jaster, B. Fitzner, D. Koczan, H.-J. Thiesen, A. Glass, D. Winder, S. Liebe, et al. Generation and characterization of immortalized rat pancreatic stellate cells Am J Physiol Gastrointest Liver Physiol, July 1, 2004; 287(1): G211 - G219. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ohnishi, T. Miyata, H. Yasuda, Y. Satoh, K. Hanatsuka, H. Kita, A. Ohashi, K. Tamada, N. Makita, T. Iiri, et al. Distinct Roles of Smad2-, Smad3-, and ERK-dependent Pathways in Transforming Growth Factor-{beta}1 Regulation of Pancreatic Stellate Cellular Functions J. Biol. Chem., March 5, 2004; 279(10): 8873 - 8878. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yamada, A. Kuno, K. Masuda, K. Ogawa, M. Sogawa, S. Nakamura, T. Ando, H. Sano, T. Nakazawa, H. Ohara, et al. Candesartan, an Angiotensin II Receptor Antagonist, Suppresses Pancreatic Inflammation and Fibrosis in Rats J. Pharmacol. Exp. Ther., October 1, 2003; 307(1): 17 - 23. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N Ohnishi, T Miyata, H Ohnishi, H Yasuda, K Tamada, N Ueda, H Mashima, and K Sugano Activin A is an autocrine activator of rat pancreatic stellate cells: potential therapeutic role of follistatin for pancreatic fibrosis Gut, October 1, 2003; 52(10): 1487 - 1493. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P A Phillips, M J Wu, R K Kumar, E Doherty, J A McCarroll, S Park, R C Pirola, J S Wilson, and M V Apte Cell migration: a novel aspect of pancreatic stellate cell biology Gut, May 1, 2003; 52(5): 677 - 682. [Abstract] [Full Text]
|
|
|
|
|
|
P A Phillips, J A McCarroll, S Park, M-J Wu, R Pirola, M Korsten, J S Wilson, and M V Apte Rat pancreatic stellate cells secrete matrix metalloproteinases: implications for extracellular matrix turnover Gut, February 1, 2003; 52(2): 275 - 282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Masamune, M. Satoh, K. Kikuta, Y. Sakai, A. Satoh, and T. Shimosegawa Inhibition of p38 Mitogen-Activated Protein Kinase Blocks Activation of Rat Pancreatic Stellate Cells J. Pharmacol. Exp. Ther., January 1, 2003; 304(1): 8 - 14. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A Zimmermann, B Gloor, A Kappeler, W Uhl, H Friess, and M W Buchler Pancreatic stellate cells contribute to regeneration early after acute necrotising pancreatitis in humans Gut, October 1, 2002; 51(4): 574 - 578. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R Jaster, G Sparmann, J Emmrich, and S Liebe Extracellular signal regulated kinases are key mediators of mitogenic signals in rat pancreatic stellate cells Gut, October 1, 2002; 51(4): 579 - 584. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Klonowski-Stumpe, R. Fischer, R. Reinehr, R. Luthen, and D. Haussinger Apoptosis in activated rat pancreatic stellate cells Am J Physiol Gastrointest Liver Physiol, September 1, 2002; 283(3): G819 - G826. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Masamune, K. Kikuta, M. Satoh, A. Satoh, and T. Shimosegawa Alcohol Activates Activator Protein-1 and Mitogen-Activated Protein Kinases in Rat Pancreatic Stellate Cells J. Pharmacol. Exp. Ther., July 1, 2002; 302(1): 36 - 42. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Demols, J.-L. Van Laethem, E. Quertinmont, C. Degraef, M. Delhaye, A. Geerts, and J. Deviere Endogenous interleukin-10 modulates fibrosis and regeneration in experimental chronic pancreatitis Am J Physiol Gastrointest Liver Physiol, June 1, 2002; 282(6): G1105 - G1112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. W.-T. Shek, R. C. Benyon, F. M. Walker, P. R. McCrudden, S. L. F. Pender, E. J. Williams, P. A. Johnson, C. D. Johnson, A. C. Bateman, D. R. Fine, et al. Expression of Transforming Growth Factor-{beta}1 by Pancreatic Stellate Cells and Its Implications for Matrix Secretion and Turnover in Chronic Pancreatitis Am. J. Pathol., May 1, 2002; 160(5): 1787 - 1798. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P Mews, P Phillips, R Fahmy, M Korsten, R Pirola, J Wilson, and M Apte Pancreatic stellate cells respond to inflammatory cytokines: potential role in chronic pancreatitis Gut, April 1, 2002; 50(4): 535 - 541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Masamune, K. Kikuta, M. Satoh, Y. Sakai, A. Satoh, and T. Shimosegawa Ligands of Peroxisome Proliferator-activated Receptor-gamma Block Activation of Pancreatic Stellate Cells J. Biol. Chem., January 4, 2002; 277(1): 141 - 147. [Abstract] [Full Text]
|
|
|
|
 |
|
 C. L. Pin, J. M. Rukstalis, C. Johnson, and S. F. Konieczny The bHLH transcription factor Mist1 is required to maintain exocrine pancreas cell organization and acinar cell identity J. Cell Biol., November 12, 2001; 155(4): 519 - 530. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Schneider, A. Schmid-Kotsas, J. Zhao, H. Weidenbach, R. M. Schmid, A. Menke, G. Adler, J. Waltenberger, A. Grunert, and M. G. Bachem Identification of mediators stimulating proliferation and matrix synthesis of rat pancreatic stellate cells Am J Physiol Cell Physiol, August 1, 2001; 281(2): C532 - C543. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Yoshikawa, Y. Kihara, M. Taguchi, T. Yamaguchi, H. Nakamura, and M. Otsuki Role of TGF-beta 1 in the development of pancreatic fibrosis in Otsuka Long-Evans Tokushima Fatty rats Am J Physiol Gastrointest Liver Physiol, March 1, 2002; 282(3): G549 - G558. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
