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Knockout of immunoproteasome subunit β2i ameliorates cardiac fibrosis and inflammation in DOCA/Salt hypertensive mice.

Abstract：

:The immunoproteasome is a multicatalytic protease complex in all eukaryotic cells, which plays a key role in regulating essential cellular processes. However, the role of immunoproteasome subunit β2i in regulation of cardiac fibrosis and inflammation in deoxycorticosterone-acetate (DOCA)/salt mice remains unknown. Wild-type (WT) and β2i knockout (KO) mice were subjected to uninephrectomy and DOCA/salt treatment for 21 days. Blood pressure was measured by the tail-cuff system. Cardiac function and remodeling were examined by echocardiography, hematoxylin-eosin (H&E) and Masson's trichrome staining. The gene and protein expressions were detected by quantitative real-time PCR, and Western blot analysis. After 21 days, DOCA/salt treatment significantly up-regulated the expression of β2i mRNA and protein in the hearts. Moreover, systolic blood pressure and heart weight/body weight (HW/BW) ratio were significantly higher in DOCA/salt mice than in sham groups, and these effects were markedly reversed in β2i knockout mice. Importantly, DOCA/salt-induced cardiac fibrosis, inflammation and the expression of collagen I, collagen III, α-SMA, IL-1β, IL-6 and TNF-α in the wild-type hearts, which were markedly attenuated by β2i knockout. These beneficial effects were due, at least in part, to the inhibition of IκBα/NF-κB and TGF-β1/Smad2/3 signaling pathways. Collectively, these findings indicate that knockout of β2i ameliorates DOCA/salt-induced cardiac fibrosis and inflammation, and may be a novel potential therapeutic target for hypertensive heart diseases.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Yan W,Bi HL,Liu LX,Li NN,Liu Y,Du J,Wang HX,Li HH

doi

10.1016/j.bbrc.2017.05.011

subject

Has Abstract

pub_date

2017-08-19 00:00:00

pages

84-90

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(17)30857-4

journal_volume

490

pub_type

杂志文章

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