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Activated protein C, an anticoagulant polypeptide, ameliorates severe acute pancreatitis via regulation of mitogen-activated protein kinases

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Abstract

Background

Our aim was to investigate the changes of mitogen-activated protein kinases (MAPKs) by activated protein C (APC) treatment in rats with severe acute pancreatitis (SAP), and relate them to changes in SAP severity, thus providing evidence for developing clinical therapies.

Methods

Sprague-Dawley rats were given an intravenous injection of saline (SAP group), APC (50 µg/kg or 10 µg/kg), or CNI1493 just before SAP induction. One group of rats underwent a sham operation (control group). Experimental samples were harvested 16 h after SAP induction. The gene expression of pancreatic MAPKs was evaluated by cDNA microarrays. The mRNA and protein/phosphorylated protein levels of p38 MAPK, extracellular signal-regulated protein kinase (ERK) 1/2, and c-Jun N-terminal kinase (JNK) and the protein levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β were determined in pancreatic tissue. The severity of disease was evaluated by pancreatic histology, the pancreatic wet/dry weight ratio, and the serum amylase level.

Results

In rats treated with APC (50 µg/kg) or CNI1493, the severity of pancreatitis and expression of pancreatic TNF-α and IL-1β proteins were attenuated by the decreased expression and activity of p38 MAPK and JNK (vs. the SAP group, P < 0.01). The expression and activity of ERK1/2 were increased in APC-treated rats, especially in the group treated with APC 50 µg/kg (vs. the SAP or CNI1493-treated group, P < 0.01, respectively).

Conclusions

Inhibition of expression of pancreatic p38 MAPK and JNK and upregulation of ERK1/2 expression by APC treatment may protect against pancreatic injury, thus ameliorating severity of the disease.

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Authors and Affiliations

  1. Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China

    Ping Chen, Yongping Zhang, Minmin Qiao & Yaozong Yuan

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  1. Ping Chen
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  2. Yongping Zhang
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  3. Minmin Qiao
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  4. Yaozong Yuan
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Chen, P., Zhang, Y., Qiao, M. et al. Activated protein C, an anticoagulant polypeptide, ameliorates severe acute pancreatitis via regulation of mitogen-activated protein kinases. J Gastroenterol 42, 887–896 (2007). https://doi.org/10.1007/s00535-007-2104-2

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  • DOI: https://doi.org/10.1007/s00535-007-2104-2

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