Potentiation of Psoriasis-Like Inflammation by PCSK9.
Animals
Apoptosis
Blotting, Western
Cell Line
Cell Proliferation
Disease Models, Animal
Female
Gene Expression Regulation
Humans
Inflammation
/ genetics
Keratinocytes
/ metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Proprotein Convertase 9
/ biosynthesis
Psoriasis
/ genetics
RNA
/ genetics
Skin
/ metabolism
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:
04 2019
04 2019
Historique:
received:
08
12
2017
revised:
19
07
2018
accepted:
27
07
2018
pubmed:
6
11
2018
medline:
3
4
2020
entrez:
6
11
2018
Statut:
ppublish
Résumé
Psoriasis is a systemic inflammatory disease, associated with metabolic disorders, including high level of low-density lipoprotein. PCSK9, which promotes the degradation of low-density lipoprotein receptors and, therefore, the increased concentration of circulating low-density lipoprotein, is also involved in inflammation. This study aims to examine the role of PCSK9 in psoriasis and to investigate the potential of topically applying small interfering RNA targeting Pcsk9 as a psoriasis treatment. We investigated the expression of PCSK9 in lesions of psoriasis patients and imiquimod-induced psoriatic reactions in Pcsk9-knockout and Pcsk9 small interfering RNA-treated mice, and we also used cultured human keratinocytes to investigate the role of PCSK9 in regulating cell proliferation and apoptosis. We found that PCSK9 is overexpressed in psoriatic lesions and that suppressing Pcsk9 can decrease the inflammatory reaction induced by imiquimod treatment and inhibit hyperproliferation of keratinocytes. We also found that suppressing PCSK9 can significantly alter the cell cycle and induce apoptosis of human keratinocytes. Taken together, our findings indicate that PCSK9 plays an important role in psoriasis and may be a therapeutic target.
Identifiants
pubmed: 30395847
pii: S0022-202X(18)32782-9
doi: 10.1016/j.jid.2018.07.046
pmc: PMC7546417
mid: NIHMS1633366
pii:
doi:
Substances chimiques
RNA
63231-63-0
Pcsk9 protein, mouse
EC 3.4.21.-
Proprotein Convertase 9
EC 3.4.21.-
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
859-867Subventions
Organisme : NIA NIH HHS
ID : K01 AG046432
Pays : United States
Organisme : NIA NIH HHS
ID : R03 AG046605
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG034349
Pays : United States
Informations de copyright
Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
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