Enhanced urokinase plasminogen activation in chronic pancreatitis suggests a role in its pathogenesis

H. Friess, D. Cantero, H. Graber, Hao Tang Wen Hao Tang, X. Guo, M. Kashiwagi, A. Zimmermann, L. Gold, M. Korc, M. W. Buchler

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Abstract

Background and Aims: Urokinase plasminogen activator (uPA) regulates plasmin generation from plasminogen. The aim of this study was to analyze the role of the plasminogen activator/plasmin system in chronic pancreatitis (CP). Methods: Using Northern blot analysis, in situ hybridization, and immunohistochemistry, the expression of uPA, its receptor (uPAR), plasminogen activator inhibitor 1 (PAI-1), and transforming growth factor β1 (TGF-β1) was studied in 14 patients undergoing pancreatic resection for CP. Normal control pancreatic tissue was obtained through an organ donor program. Results: Eight of 14 CP samples showed concomitant increased expression (P < 0.001) of uPA (5.2-fold), uPAR (5.9-fold), and TGF-β1 (8.8-fold) messenger RNA (mRNA) compared with normal controls. PAI-1 mRNA expression was increased (6.5-fold; P < 0.001) in all CP samples. By in situ hybridization, moderate to strong mRNA staining of all four factors was present in acinar cells, some ductal cells, and areas with ductal metaplasia in CP samples. A similar staining pattern was found by immunohistochemistry. Intense mRNA and immunostaining for all of these factors in CP samples was associated with a higher degree of pancreatic damage. Conclusions: uPA and its receptor may contribute to the lyric damage observed in CP by plasmin generation. Similarly, increased amounts of plasmin may activate latent TGF-β, thereby leading to the accumulation of fibrotic tissue.

Original languageEnglish (US)
Pages (from-to)904-913
Number of pages10
JournalGastroenterology
Volume113
Issue number3
DOIs
StatePublished - Jan 1 1997

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Friess, H., Cantero, D., Graber, H., Wen Hao Tang, H. T., Guo, X., Kashiwagi, M., Zimmermann, A., Gold, L., Korc, M., & Buchler, M. W. (1997). Enhanced urokinase plasminogen activation in chronic pancreatitis suggests a role in its pathogenesis. Gastroenterology, 113(3), 904-913. https://doi.org/10.1016/S0016-5085(97)70186-0