کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5505197 1400263 2017 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Knockout of immunoproteasome subunit β2i ameliorates cardiac fibrosis and inflammation in DOCA/Salt hypertensive mice
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Knockout of immunoproteasome subunit β2i ameliorates cardiac fibrosis and inflammation in DOCA/Salt hypertensive mice
چکیده انگلیسی

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 490, Issue 2, 19 August 2017, Pages 84-90
نویسندگان
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