RGD Reference Report - Activated protein C improves the severity of severe acute pancreatitis via up-regulating the expressions of endothelial cell protein C receptor and thrombomodulin.

General

Activated protein C improves the severity of severe acute pancreatitis via up-regulating the expressions of endothelial cell protein C receptor and thrombomodulin.
Authors:	Ping, C Yongping, Z Minmin, Q Weiyan, Y Yaozong, Y
Citation:	Ping C, etal., Dig Dis Sci. 2010 Jun;55(6):1599-609. doi: 10.1007/s10620-009-0909-y. Epub 2009 Aug 13.
RGD ID:	11100040
Pubmed:	PMID:19680809 (View Abstract at PubMed)
DOI:	DOI:10.1007/s10620-009-0909-y (Journal Full-text)
BACKGROUND AND AIMS: Activated protein C (APC) is increasingly understood to have diverse regulatory functions in inflammation. However, the exact mechanism of action remains unclear in severe acute pancreatitis (SAP). The aim of this study was to demonstrate the effects of APC on expressions of thrombomodulin (TM) and endothelial cell protein C receptor (EPCR), and its subsequent effect on the severity of SAP. METHODS: Sprague-Dawley rats were randomly divided into four groups. The rats were given intravenous injections of APC (50, 10 microg/kg, respectively, treated groups) or saline (SAP group) just before induction of SAP. One group of rats underwent only sham operation as control group. Experimental samples were harvested at 16 h after induction. The protein and mRNA levels of matrix metalloprotease 9 (MMP-9), TM, and EPCR in pancreatic tissue were investigated. Serum tumor necrosis factor alpha (TNF-alpha) and interleukin-8 (IL-8) levels were determined. The severity of disease was evaluated by histological score of pancreatic injury, wet/dry weight ratio of pancreatic tissue, and serum amylase. RESULTS: In the APC 50 microg/kg-treated group, serum TNF-alpha, IL-8, and pancreatic MMP-9 levels were decreased and the levels of pancreatic EPCR and TM were up-regulated compared with the SAP group. A significant dose-dependent relationship was found between the decreased levels of serum IL-8 and the APC-treated dosage. Furthermore, the severity of SAP was ameliorated by APC treatment. CONCLUSIONS: APC could augment the anti-coagulation and anti-inflammatory activity by up-regulating EPCR and TM expressions, thus attenuating the severity of SAP.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
Acute Experimental Pancreatitis	treatment	IDA		11100040		RGD
Acute Experimental Pancreatitis	treatment	ISO	PROC (Homo sapiens)	11100040; 11100040		RGD

Objects Annotated

Genes (Rattus norvegicus)

Proc (protein C, inactivator of coagulation factors Va and VIIIa)

Genes (Mus musculus)

Proc (protein C)

Genes (Homo sapiens)

PROC (protein C, inactivator of coagulation factors Va and VIIIa)

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Activated protein C improves the severity of severe acute pancreatitis via up-regulating the expressions of endothelial cell protein C receptor and thrombomodulin.