Inhibition of P2X7 Purinergic Receptor Ameliorates Cardiac Fibrosis by Suppressing NLRP3/IL-1β Pathway

Copyright © 2020 Junteng Zhou et al..

P2X7 purinergic receptor (P2X7R) has been implicated in several cardiovascular diseases. However, whether it regulates cardiac fibrosis remains elusive. Herein, its involvement in the development of cardiac fibrosis was examined using a transverse aortic constriction (TAC) mice model and cardiac fibroblasts (CFs) hyperstimulated by TGF-β1 for 48 hours. Results showed that TAC and TGF-β1 treatment increased the expression of P2X7R. Silencing of P2X7R expression with siP2X7R ameliorated TGF-β1 effects on fibroblasts activation. Similarly, P2X7R inhibition by Brilliant Blue G (BBG) reduced mRNA and protein levels of profibrosis markers, while the P2X7R agonist BzATP accelerated the TGF-β1-induced CFs activation. Moreover, it was found that TGF-β1-induced CFs activation was mediated by the NLRP3/IL-1β inflammasome pathway. BBG or siP2X7R treatment suppressed NLRP3/IL-1β pathway signaling. In vivo, BBG significantly alleviated TAC-induced cardiac fibrosis, cardiac dysfunction, and NLRP3/IL-1β activation. Collectively, our findings imply that suppressing P2X7R may limit cardiac fibrosis and abnormal activation of CFs.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:2020

Enthalten in:

Oxidative medicine and cellular longevity - 2020(2020) vom: 11., Seite 7956274

Sprache:

Englisch

Beteiligte Personen:

Zhou, Junteng [VerfasserIn]
Tian, Geer [VerfasserIn]
Quan, Yue [VerfasserIn]
Li, Junli [VerfasserIn]
Wang, Xiaojiao [VerfasserIn]
Wu, Wenchao [VerfasserIn]
Li, Miaoling [VerfasserIn]
Liu, Xiaojing [VerfasserIn]

Links:

Volltext

Themen:

Interleukin-1beta
Journal Article
NLR Family, Pyrin Domain-Containing 3 Protein
Purinergic P2X Receptor Antagonists
Receptors, Purinergic P2X7
Transforming Growth Factor beta1

Anmerkungen:

Date Completed 27.01.2021

Date Revised 27.01.2021

published: Electronic-eCollection

Citation Status MEDLINE

doi:

10.1155/2020/7956274

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM311447252