The plasminogen activator/plasmin system is up-regulated after acute necrotizing pancreatitis in human beings

H. Friess, R. Duarte, J. Kleeff, A. Fukuda, W. H. Tang, H. Graber, M. Schilling, A. Zimmermann, Murray Korc, M. W. Buchler

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background. Proteolysis and formation of new extracellular matrix components are important mechanisms in tissue remodeling and repair. In this study we analyzed the expression and distribution of the urokinase plasminogen activator (uPA), its membrane receptor (urokinase plasminogen activator receptor [uPAR]), and its inhibitor (plasminogen activator inhibitor-1 [PAI-1]) in acute necrotizing pancreatitis in human beings. In addition, we studied the concomitant expression of transforming growth factor-beta-1 (TGFβ1), which is activated by uPA from its precursor and is a potent regulator and stimulator of formation of extracellular matrix. Methods with immunohistochemistry and Northern blot analysis, the expression and cellular distribution of uPA, uPAR; PAI-1, and TGF-β1 were determined in 12 normal pancreata obtained from organ donors and 12 pancreatic tissues obtained from patients undergoing operation because of complications of acute necrotizing pancreatitis. Results. Northern blot analysis showed enhanced expression of uPA, uPAR, and PAI-1 in eight of 12, seven of 12, and nine of 12 necrotizing pancreatitis samples, respectively, compared with normal control samples. In addition, increased TGF-β1 mRNA expression was present in eight of 12 necrotizing pancreatitis samples. In contrast, amylase mRNA expression was markedly decreased in the samples of acute necrotizing pancreatitis. Immunohistochemistry revealed elevated uPA, uPAR; and PAI-1 immunoreactivity in the remaining acinar and ductal cells adjacent to the necrotic tissue areas. In contrast, acinar and ductal cells that were located farther from pancreatic necrosis exhibited less uPA and uPAR immunoreactivity. A similar stain g pattern in samples of necrotizing pancreatitis was found for TGF-β1. Conclusions. Up-regulation of uPA and uPAR, which activate proteolysis, might create a milieu that enhances lysis and removal of pancreatic necrosis. The increase in TGF-β1 might result from the enhanced catalytic conversion of its precursors by uPA, which subsequently might stimulate formation of extracellular matrix, formation of granulation tissue, and fibrosis.

Original languageEnglish (US)
Pages (from-to)79-86
Number of pages8
JournalSurgery
Volume124
Issue number1
DOIs
StatePublished - 1998
Externally publishedYes

Fingerprint

Acute Necrotizing Pancreatitis
Plasminogen Activators
Fibrinolysin
Urokinase-Type Plasminogen Activator
Urokinase Plasminogen Activator Receptors
Plasminogen Activator Inhibitor 1
Pancreatitis
Extracellular Matrix
Acinar Cells
Northern Blotting
Proteolysis
Necrosis
Immunohistochemistry
Messenger RNA
Granulation Tissue
Amylases
Transforming Growth Factor beta
Pancreas
Fibrosis
Coloring Agents

ASJC Scopus subject areas

  • Surgery

Cite this

Friess, H., Duarte, R., Kleeff, J., Fukuda, A., Tang, W. H., Graber, H., ... Buchler, M. W. (1998). The plasminogen activator/plasmin system is up-regulated after acute necrotizing pancreatitis in human beings. Surgery, 124(1), 79-86. https://doi.org/10.1016/S0039-6060(98)70078-9

The plasminogen activator/plasmin system is up-regulated after acute necrotizing pancreatitis in human beings. / Friess, H.; Duarte, R.; Kleeff, J.; Fukuda, A.; Tang, W. H.; Graber, H.; Schilling, M.; Zimmermann, A.; Korc, Murray; Buchler, M. W.

In: Surgery, Vol. 124, No. 1, 1998, p. 79-86.

Research output: Contribution to journalArticle

Friess, H, Duarte, R, Kleeff, J, Fukuda, A, Tang, WH, Graber, H, Schilling, M, Zimmermann, A, Korc, M & Buchler, MW 1998, 'The plasminogen activator/plasmin system is up-regulated after acute necrotizing pancreatitis in human beings', Surgery, vol. 124, no. 1, pp. 79-86. https://doi.org/10.1016/S0039-6060(98)70078-9
Friess, H. ; Duarte, R. ; Kleeff, J. ; Fukuda, A. ; Tang, W. H. ; Graber, H. ; Schilling, M. ; Zimmermann, A. ; Korc, Murray ; Buchler, M. W. / The plasminogen activator/plasmin system is up-regulated after acute necrotizing pancreatitis in human beings. In: Surgery. 1998 ; Vol. 124, No. 1. pp. 79-86.
@article{75326d470e544d1d924e8ee84e229421,
title = "The plasminogen activator/plasmin system is up-regulated after acute necrotizing pancreatitis in human beings",
abstract = "Background. Proteolysis and formation of new extracellular matrix components are important mechanisms in tissue remodeling and repair. In this study we analyzed the expression and distribution of the urokinase plasminogen activator (uPA), its membrane receptor (urokinase plasminogen activator receptor [uPAR]), and its inhibitor (plasminogen activator inhibitor-1 [PAI-1]) in acute necrotizing pancreatitis in human beings. In addition, we studied the concomitant expression of transforming growth factor-beta-1 (TGFβ1), which is activated by uPA from its precursor and is a potent regulator and stimulator of formation of extracellular matrix. Methods with immunohistochemistry and Northern blot analysis, the expression and cellular distribution of uPA, uPAR; PAI-1, and TGF-β1 were determined in 12 normal pancreata obtained from organ donors and 12 pancreatic tissues obtained from patients undergoing operation because of complications of acute necrotizing pancreatitis. Results. Northern blot analysis showed enhanced expression of uPA, uPAR, and PAI-1 in eight of 12, seven of 12, and nine of 12 necrotizing pancreatitis samples, respectively, compared with normal control samples. In addition, increased TGF-β1 mRNA expression was present in eight of 12 necrotizing pancreatitis samples. In contrast, amylase mRNA expression was markedly decreased in the samples of acute necrotizing pancreatitis. Immunohistochemistry revealed elevated uPA, uPAR; and PAI-1 immunoreactivity in the remaining acinar and ductal cells adjacent to the necrotic tissue areas. In contrast, acinar and ductal cells that were located farther from pancreatic necrosis exhibited less uPA and uPAR immunoreactivity. A similar stain g pattern in samples of necrotizing pancreatitis was found for TGF-β1. Conclusions. Up-regulation of uPA and uPAR, which activate proteolysis, might create a milieu that enhances lysis and removal of pancreatic necrosis. The increase in TGF-β1 might result from the enhanced catalytic conversion of its precursors by uPA, which subsequently might stimulate formation of extracellular matrix, formation of granulation tissue, and fibrosis.",
author = "H. Friess and R. Duarte and J. Kleeff and A. Fukuda and Tang, {W. H.} and H. Graber and M. Schilling and A. Zimmermann and Murray Korc and Buchler, {M. W.}",
year = "1998",
doi = "10.1016/S0039-6060(98)70078-9",
language = "English (US)",
volume = "124",
pages = "79--86",
journal = "Surgery",
issn = "0039-6060",
publisher = "Mosby Inc.",
number = "1",

}

TY - JOUR

T1 - The plasminogen activator/plasmin system is up-regulated after acute necrotizing pancreatitis in human beings

AU - Friess, H.

AU - Duarte, R.

AU - Kleeff, J.

AU - Fukuda, A.

AU - Tang, W. H.

AU - Graber, H.

AU - Schilling, M.

AU - Zimmermann, A.

AU - Korc, Murray

AU - Buchler, M. W.

PY - 1998

Y1 - 1998

N2 - Background. Proteolysis and formation of new extracellular matrix components are important mechanisms in tissue remodeling and repair. In this study we analyzed the expression and distribution of the urokinase plasminogen activator (uPA), its membrane receptor (urokinase plasminogen activator receptor [uPAR]), and its inhibitor (plasminogen activator inhibitor-1 [PAI-1]) in acute necrotizing pancreatitis in human beings. In addition, we studied the concomitant expression of transforming growth factor-beta-1 (TGFβ1), which is activated by uPA from its precursor and is a potent regulator and stimulator of formation of extracellular matrix. Methods with immunohistochemistry and Northern blot analysis, the expression and cellular distribution of uPA, uPAR; PAI-1, and TGF-β1 were determined in 12 normal pancreata obtained from organ donors and 12 pancreatic tissues obtained from patients undergoing operation because of complications of acute necrotizing pancreatitis. Results. Northern blot analysis showed enhanced expression of uPA, uPAR, and PAI-1 in eight of 12, seven of 12, and nine of 12 necrotizing pancreatitis samples, respectively, compared with normal control samples. In addition, increased TGF-β1 mRNA expression was present in eight of 12 necrotizing pancreatitis samples. In contrast, amylase mRNA expression was markedly decreased in the samples of acute necrotizing pancreatitis. Immunohistochemistry revealed elevated uPA, uPAR; and PAI-1 immunoreactivity in the remaining acinar and ductal cells adjacent to the necrotic tissue areas. In contrast, acinar and ductal cells that were located farther from pancreatic necrosis exhibited less uPA and uPAR immunoreactivity. A similar stain g pattern in samples of necrotizing pancreatitis was found for TGF-β1. Conclusions. Up-regulation of uPA and uPAR, which activate proteolysis, might create a milieu that enhances lysis and removal of pancreatic necrosis. The increase in TGF-β1 might result from the enhanced catalytic conversion of its precursors by uPA, which subsequently might stimulate formation of extracellular matrix, formation of granulation tissue, and fibrosis.

AB - Background. Proteolysis and formation of new extracellular matrix components are important mechanisms in tissue remodeling and repair. In this study we analyzed the expression and distribution of the urokinase plasminogen activator (uPA), its membrane receptor (urokinase plasminogen activator receptor [uPAR]), and its inhibitor (plasminogen activator inhibitor-1 [PAI-1]) in acute necrotizing pancreatitis in human beings. In addition, we studied the concomitant expression of transforming growth factor-beta-1 (TGFβ1), which is activated by uPA from its precursor and is a potent regulator and stimulator of formation of extracellular matrix. Methods with immunohistochemistry and Northern blot analysis, the expression and cellular distribution of uPA, uPAR; PAI-1, and TGF-β1 were determined in 12 normal pancreata obtained from organ donors and 12 pancreatic tissues obtained from patients undergoing operation because of complications of acute necrotizing pancreatitis. Results. Northern blot analysis showed enhanced expression of uPA, uPAR, and PAI-1 in eight of 12, seven of 12, and nine of 12 necrotizing pancreatitis samples, respectively, compared with normal control samples. In addition, increased TGF-β1 mRNA expression was present in eight of 12 necrotizing pancreatitis samples. In contrast, amylase mRNA expression was markedly decreased in the samples of acute necrotizing pancreatitis. Immunohistochemistry revealed elevated uPA, uPAR; and PAI-1 immunoreactivity in the remaining acinar and ductal cells adjacent to the necrotic tissue areas. In contrast, acinar and ductal cells that were located farther from pancreatic necrosis exhibited less uPA and uPAR immunoreactivity. A similar stain g pattern in samples of necrotizing pancreatitis was found for TGF-β1. Conclusions. Up-regulation of uPA and uPAR, which activate proteolysis, might create a milieu that enhances lysis and removal of pancreatic necrosis. The increase in TGF-β1 might result from the enhanced catalytic conversion of its precursors by uPA, which subsequently might stimulate formation of extracellular matrix, formation of granulation tissue, and fibrosis.

UR - http://www.scopus.com/inward/record.url?scp=0031902081&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031902081&partnerID=8YFLogxK

U2 - 10.1016/S0039-6060(98)70078-9

DO - 10.1016/S0039-6060(98)70078-9

M3 - Article

C2 - 9663255

AN - SCOPUS:0031902081

VL - 124

SP - 79

EP - 86

JO - Surgery

JF - Surgery

SN - 0039-6060

IS - 1

ER -