Document Detail


Urokinase-type plasminogen activator up-regulates its own expression by endothelial cells and monocytes via the u-PAR pathway.
MedLine Citation:
PMID:  11672584     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Signal transduction by urokinase-type plasminogen activator (u-PA) bound to its cell receptor has been well established. In the present study, we found, for the first time to our knowledge, that u-PA promotes its own synthesis by endothelial cells and monocytes. This phenomenon was characterized and shown to involve the u-PA receptor (u-PAR) pathway. The finding may be of general importance, since most cells that express u-PAR also produce u-PA. Human umbilical vein endothelial cells (HUVECs), U937 monocytes, and human peripheral blood monocytes (PFMCs) were incubated with diisopropylfluorophosphate (DFP)-pretreated u-PA, the amino-terminal fragment (ATF) of u-PA, or the kringle domain. A threefold up-regulation of u-PA secretion and synthesis by u-PA or ATF was found. The predominant effect was expressed in HUVECs, in which u-PA mRNA was also up-regulated. The u-PA kringle domain had no effect on u-PA synthesis, leading to the conclusion that the EGF domain was responsible. This was also consistent with the additional finding that the u-PAR, to which the EGF domain binds, was necessary for the up-regulation. The results indicate that u-PA up-regulates itself via its EGF domain and u-PAR. The possibilities that the results were related to displacement of receptor-bound u-PA or the blocking of u-PA incorporation into the cells were excluded. A modest up-regulation of u-PAR was also associated with this phenomenon.
Authors:
C Li; J Zhang; Y Jiang; V Gurewich; Y Chen; J N Liu
Related Documents :
19339244 - Frs2 via fibroblast growth factor receptor 1 is required for platelet-derived growth fa...
18086474 - Gremlin promotes vascular smooth muscle cell proliferation and migration.
9227364 - Control of extracellular matrix remodelling within ovarian tissues: localization and re...
20379844 - Platelet-derived growth factor-d contributes to aggressiveness of breast cancer cells b...
15519644 - Pirfenidone inhibits the induction of inos stimulated by interleukin-1beta at a step of...
15652234 - Inhibition of interleukin-12 expression in diltiazem-treated dendritic cells through th...
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Thrombosis research     Volume:  103     ISSN:  0049-3848     ISO Abbreviation:  Thromb. Res.     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-10-23     Completed Date:  2002-03-18     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0326377     Medline TA:  Thromb Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  221-32     Citation Subset:  IM    
Affiliation:
Institute of Molecular Medicine, Nanjing University, Nanjing 10008, China.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Cell Line
Dose-Response Relationship, Drug
Endothelium, Vascular / cytology,  enzymology*
Feedback, Physiological*
Humans
Kinetics
Mannose-Binding Lectins*
Membrane Glycoproteins / physiology*
Monocytes / enzymology*
Peptide Fragments / pharmacology
Protein Structure, Tertiary / physiology
RNA, Messenger / metabolism
Receptors, Cell Surface / physiology*
Umbilical Veins / cytology
Up-Regulation / drug effects
Urokinase-Type Plasminogen Activator / biosynthesis*,  genetics,  pharmacology
Chemical
Reg. No./Substance:
0/MRC2 protein, human; 0/Mannose-Binding Lectins; 0/Membrane Glycoproteins; 0/Peptide Fragments; 0/RNA, Messenger; 0/Receptors, Cell Surface; EC 3.4.21.73/Urokinase-Type Plasminogen Activator

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Activated protein C induction of MCP-1 in human endothelial cells: a possible role for endothelial c...
Next Document:  Daunorubicin inhibits gene expression of cyclooxygenase-2 in vascular smooth muscle cells.