Knockdown of HIPK2 Attenuates Angiotensin II-Induced Cardiac Fibrosis in Cardiac Fibroblasts.
Journal
Journal of cardiovascular pharmacology
ISSN: 1533-4023
Titre abrégé: J Cardiovasc Pharmacol
Pays: United States
ID NLM: 7902492
Informations de publication
Date de publication:
01 07 2022
01 07 2022
Historique:
received:
04
01
2022
accepted:
20
04
2022
pubmed:
7
5
2022
medline:
9
7
2022
entrez:
6
5
2022
Statut:
epublish
Résumé
Homeodomain-interacting protein kinase-2 (HIPK2), a member of an evolutionary conserved family of serine/threonine kinases, has been observed to be involved in the pathogenesis of fibrotic diseases. However, its role in cardiac fibrosis remains unclear. In this study, we assessed the effect of HIPK2 on cardiac fibroblasts (CFs) in response to angiotensin II (Ang II) stimulation. The results indicated that HIPK2 expression was significantly increased in Ang II-induced CFs in a dose-dependent manner. Then, HIPK2 was knocked down in CFs to evaluate the roles of HIPK2. Knockdown of HIPK2 suppressed cell proliferation and migration in Ang II-induced CFs. The Ang II-caused increase in expression of α-smooth muscle actin, a hallmark of myofibroblast differentiation, was decreased by knockdown of HIPK2. HIPK2 knockdown also reduced extracellular matrix production including type I collagen and connective tissue growth factor. Furthermore, knockdown of HIPK2 blocked the activation of TGF-β1/Smad pathway in Ang II-induced CFs. These data suggested that HIPK2 knockdown prevented the Ang II-induced activation of CFs through inhibiting TGF-β1/Smad pathway, indicating HIPK2 might be an antifibrosis target for the treatment of cardiac fibrosis.
Identifiants
pubmed: 35522151
doi: 10.1097/FJC.0000000000001292
pii: 00005344-202207000-00013
doi:
Substances chimiques
Carrier Proteins
0
Transforming Growth Factor beta1
0
Angiotensin II
11128-99-7
HIPK2 protein, human
EC 2.7.1.-
Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
125-131Informations de copyright
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest.
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