Inhibition of the DNA Damage Response Attenuates Ectopic Calcification in Pseudoxanthoma Elasticum.
Journal
The Journal of investigative dermatology
ISSN: 1523-1747
Titre abrégé: J Invest Dermatol
Pays: United States
ID NLM: 0426720
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
21
10
2021
revised:
25
01
2022
accepted:
28
01
2022
pubmed:
11
2
2022
medline:
27
7
2022
entrez:
10
2
2022
Statut:
ppublish
Résumé
Pseudoxanthoma elasticum (PXE) is a heritable ectopic calcification disorder with multiorgan clinical manifestations. The gene at default, ABCC6, encodes an efflux transporter, ABCC6, which is a critical player regulating the homeostasis of inorganic pyrophosphate, a potent endogenous anticalcification factor. Previous studies suggested that systemic inorganic pyrophosphate deficiency is the major but not the exclusive cause of ectopic calcification in PXE. In this study, we show that the DNA damage response (DDR) and poly(ADP-ribose) (PAR) pathways are involved locally in PXE at sites of ectopic calcification. Genetic inhibition of PAR polymerase 1 gene PARP1, the predominant PAR-producing enzyme, showed a 54% reduction of calcification in the muzzle skin in Abcc6
Identifiants
pubmed: 35143822
pii: S0022-202X(22)00092-6
doi: 10.1016/j.jid.2022.01.022
pmc: PMC9329183
mid: NIHMS1779336
pii:
doi:
Substances chimiques
Abcc6 protein, mouse
0
Diphosphates
0
Multidrug Resistance-Associated Proteins
0
Parp1 protein, mouse
EC 2.4.2.30
Poly (ADP-Ribose) Polymerase-1
EC 2.4.2.30
Minocycline
FYY3R43WGO
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
2140-2148.e1Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR072695
Pays : United States
Organisme : NIAMS NIH HHS
ID : R21 AR077332
Pays : United States
Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
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