P-selectin deficiency promotes liver senescence in sickle cell disease mice.
Journal
Blood
ISSN: 1528-0020
Titre abrégé: Blood
Pays: United States
ID NLM: 7603509
Informations de publication
Date de publication:
13 05 2021
13 05 2021
Historique:
received:
02
11
2020
accepted:
01
02
2021
pubmed:
24
2
2021
medline:
15
12
2021
entrez:
23
2
2021
Statut:
ppublish
Résumé
Sickle cell disease (SCD) is caused by a homozygous mutation in the β-globin gene, which leads to erythrocyte sickling, vasoocclusion, and intense hemolysis. P-selectin inhibition has been shown to prevent vasoocclusive events in patients with SCD; however, the chronic effect of P-selectin inhibition in SCD remains to be determined. Here, we used quantitative liver intravital microscopy in our recently generated P-selectin-deficient SCD mice to show that chronic P-selectin deficiency attenuates liver ischemia but fails to prevent hepatobiliary injury. Remarkably, we find that this failure in resolution of hepatobiliary injury in P-selectin-deficient SCD mice is associated with the increase in cellular senescence and reduced epithelial cell proliferation in the liver. These findings highlight the importance of investigating the long-term effects of chronic P-selectin inhibition therapy on liver pathophysiology in patients with SCD.
Identifiants
pubmed: 33619560
pii: S0006-4971(21)00413-4
doi: 10.1182/blood.2020009779
pmc: PMC8120139
doi:
Substances chimiques
Membrane Proteins
0
P-Selectin
0
Heme Oxygenase-1
EC 1.14.14.18
Hmox1 protein, mouse
EC 1.14.14.18
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Video-Audio Media
Langues
eng
Sous-ensembles de citation
IM
Pagination
2676-2680Subventions
Organisme : NIDDK NIH HHS
ID : K01 DK125617
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL128297
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL141080
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : ErratumIn
Informations de copyright
© 2021 by The American Society of Hematology.
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