PMID- 32238698
OWN - NLM
STAT- MEDLINE
DCOM- 20200922
LR  - 20200922
IS  - 1880-3989 (Electronic)
IS  - 0388-1350 (Linking)
VI  - 45
IP  - 4
DP  - 2020
TI  - Nuclear factor erythroid 2-related factor 2 (NRF2) is a negative regulator of 
      tissue plasminogen activator synthesis in cultured human vascular endothelial 
      EA.hy926 cells.
PG  - 237-243
LID - 10.2131/jts.45.237 [doi]
AB  - Blood coagulation and the fibrinolytic system contribute to vascular lesions. 
      Fibrinolysis in normal circulating blood strongly depends on the balance between 
      tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 
      (PAI-1) secreted from vascular endothelial cells; however, the mechanisms by 
      which endothelial fibrinolysis is regulated remain to be fully understood. In the 
      present study, human vascular endothelial EA.hy926 cells were transfected with 
      small interfering RNA for nuclear factor erythroid 2-related factor 2 (NRF2) and 
      the expression of t-PA and PAI-1 and fibrinolytic activity in the conditioned 
      medium were examined. EA.hy926 cells were also treated with sulforaphane, an NRF2 
      activator, and fibrinolytic activity was examined to confirm the NRF2 signaling 
      pathway's effect. Enhanced fibrinolytic activity in the conditioned medium was 
      observed in association with increased expression and secretion levels of t-PA in 
      NRF2 knockdown EA.hy926 cells. However, sulforaphane inhibited fibrinolytic 
      activity and t-PA synthesis in EA.hy926 cells without any cell damage. The 
      expression level of PAI-1 did not change in either NRF2 knockdown or sulforaphane 
      treated cells. These results suggest that transcription factor NRF2 may play a 
      role in down-regulating endothelial t-PA synthesis and fibrinolytic activity.
FAU - Takahashi, Tsutomu
AU  - Takahashi T
AD  - Department of Environmental Health, School of Pharmacy, Tokyo University of 
      Pharmacy and Life Sciences.
FAU - Nakano, Tsuyoshi
AU  - Nakano T
AD  - Department of Environmental Health, School of Pharmacy, Tokyo University of 
      Pharmacy and Life Sciences.
FAU - Katoh, Go
AU  - Katoh G
AD  - Department of Environmental Health, School of Pharmacy, Tokyo University of 
      Pharmacy and Life Sciences.
FAU - Shinoda, Yo
AU  - Shinoda Y
AD  - Department of Environmental Health, School of Pharmacy, Tokyo University of 
      Pharmacy and Life Sciences.
FAU - Yamamoto, Chika
AU  - Yamamoto C
AD  - Department of Environmental Health, Faculty of Pharmaceutical Sciences, Toho 
      University.
FAU - Yoshida, Eiko
AU  - Yoshida E
AD  - Department of Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo 
      University of Science.
FAU - Kaji, Toshiyuki
AU  - Kaji T
AD  - Department of Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo 
      University of Science.
FAU - Fujiwara, Yasuyuki
AU  - Fujiwara Y
AD  - Department of Environmental Health, School of Pharmacy, Tokyo University of 
      Pharmacy and Life Sciences.
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - J Toxicol Sci
JT  - The Journal of toxicological sciences
JID - 7805798
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (SERPINE1 protein, human)
RN  - EC 3.4.21.68 (Tissue Plasminogen Activator)
SB  - IM
MH  - Cells, Cultured
MH  - Down-Regulation/*genetics
MH  - Endothelial Cells/*metabolism
MH  - Fibrinolysis/genetics
MH  - Gene Expression/genetics
MH  - Humans
MH  - NF-E2-Related Factor 2/*physiology
MH  - Plasminogen Activator Inhibitor 1/genetics/metabolism
MH  - Tissue Plasminogen Activator/genetics/*metabolism
OTO - NOTNLM
OT  - Fibrinolysis
OT  - Human endothelial cell line EA.hy926
OT  - NRF2
OT  - Plasminogen activator
OT  - Vascular
EDAT- 2020/04/03 06:00
MHDA- 2020/09/23 06:00
CRDT- 2020/04/03 06:00
PHST- 2020/04/03 06:00 [entrez]
PHST- 2020/04/03 06:00 [pubmed]
PHST- 2020/09/23 06:00 [medline]
AID - 10.2131/jts.45.237 [doi]
PST - ppublish
SO  - J Toxicol Sci. 2020;45(4):237-243. doi: 10.2131/jts.45.237.