An ATF6-tPA pathway in hepatocytes contributes to systemic fibrinolysis and is repressed by DACH1.
Activating Transcription Factor 6
/ genetics
Animals
Cells, Cultured
Eye Proteins
/ genetics
Female
Fibrinolysis
/ drug effects
Fibrinolytic Agents
/ pharmacology
Hepatocytes
/ drug effects
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Thrombosis
/ drug therapy
Tissue Plasminogen Activator
/ genetics
Transcription Factors
/ genetics
Journal
Blood
ISSN: 1528-0020
Titre abrégé: Blood
Pays: United States
ID NLM: 7603509
Informations de publication
Date de publication:
14 02 2019
14 02 2019
Historique:
received:
19
07
2018
accepted:
13
11
2018
pubmed:
7
12
2018
medline:
19
10
2019
entrez:
4
12
2018
Statut:
ppublish
Résumé
Tissue-type plasminogen activator (tPA) is a major mediator of fibrinolysis and, thereby, prevents excessive coagulation without compromising hemostasis. Studies on tPA regulation have focused on its acute local release by vascular cells in response to injury or other stimuli. However, very little is known about sources, regulation, and fibrinolytic function of noninjury-induced systemic plasma tPA. We explore the role and regulation of hepatocyte-derived tPA as a source of basal plasma tPA activity and as a contributor to fibrinolysis after vascular injury. We show that hepatocyte tPA is downregulated by a pathway in which the corepressor DACH1 represses ATF6, which is an inducer of the tPA gene
Identifiants
pubmed: 30504459
pii: S0006-4971(20)42798-3
doi: 10.1182/blood-2018-07-864843
pmc: PMC6376283
doi:
Substances chimiques
ATF6 protein, human
0
Activating Transcription Factor 6
0
Atf6 protein, mouse
0
DACH1 protein, human
0
Dach1 protein, mouse
0
Eye Proteins
0
Fibrinolytic Agents
0
Transcription Factors
0
PLAT protein, human
EC 3.4.21.68
Tissue Plasminogen Activator
EC 3.4.21.68
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
743-753Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL123098
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL135789
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK064819
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007343
Pays : United States
Organisme : NIDDK NIH HHS
ID : K99 DK115778
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL087123
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK063608
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA132115
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK106045
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL121131
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR027050
Pays : United States
Organisme : NLM NIH HHS
ID : HHSN276201200017C
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA013696
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2019 by The American Society of Hematology.
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