PMID- 11672584
OWN - NLM
STAT- MEDLINE
DCOM- 20020318
LR  - 20190727
IS  - 0049-3848 (Print)
IS  - 0049-3848 (Linking)
VI  - 103
IP  - 3
DP  - 2001 Aug 1
TI  - Urokinase-type plasminogen activator up-regulates its own expression by 
      endothelial cells and monocytes via the u-PAR pathway.
PG  - 221-32
AB  - 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.
FAU - Li, C
AU  - Li C
AD  - Institute of Molecular Medicine, Nanjing University, Nanjing 10008, China.
FAU - Zhang, J
AU  - Zhang J
FAU - Jiang, Y
AU  - Jiang Y
FAU - Gurewich, V
AU  - Gurewich V
FAU - Chen, Y
AU  - Chen Y
FAU - Liu, J N
AU  - Liu JN
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Thromb Res
JT  - Thrombosis research
JID - 0326377
RN  - 0 (MRC2 protein, human)
RN  - 0 (Mannose-Binding Lectins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cell Surface)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
SB  - IM
MH  - Cell Line
MH  - Dose-Response Relationship, Drug
MH  - Endothelium, Vascular/cytology/*enzymology
MH  - *Feedback, Physiological
MH  - Humans
MH  - Kinetics
MH  - *Mannose-Binding Lectins
MH  - Membrane Glycoproteins/*physiology
MH  - Monocytes/*enzymology
MH  - Peptide Fragments/pharmacology
MH  - Protein Structure, Tertiary/physiology
MH  - RNA, Messenger/metabolism
MH  - Receptors, Cell Surface/*physiology
MH  - Umbilical Veins/cytology
MH  - Up-Regulation/drug effects
MH  - Urokinase-Type Plasminogen Activator/*biosynthesis/genetics/pharmacology
EDAT- 2001/10/24 10:00
MHDA- 2002/03/19 10:01
CRDT- 2001/10/24 10:00
PHST- 2001/10/24 10:00 [pubmed]
PHST- 2002/03/19 10:01 [medline]
PHST- 2001/10/24 10:00 [entrez]
AID - S0049-3848(01)00322-X [pii]
AID - 10.1016/s0049-3848(01)00322-x [doi]
PST - ppublish
SO  - Thromb Res. 2001 Aug 1;103(3):221-32. doi: 10.1016/s0049-3848(01)00322-x.