کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8258765 | 1534613 | 2018 | 55 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Endogenous osteopontin induces myocardial CCL5 and MMP-2 activation that contributes to inflammation and cardiac remodeling in a mouse model of chronic Chagas heart disease
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
MMP-2Jun NH2-terminal kinaseTPA-responsive elementOPNCcl5AP-1DPIJnkMAPK - MAPKOsteopontin - استئوپنتینinflammation - التهاب( توروم) standard deviation - انحراف معیارCardiac remodeling - بازسازی قلبANOVA - تحلیل واریانس Analysis of varianceone-way analysis of variance - تحلیل واریانس یک راههTrypanosoma cruzi - تریپانوزوم کروزیdays post infection - روز پس از عفونتTRE - سهMatrix metalloproteinase-2 - ماتریکس متالوپروتئیناز-2wild-type - نوع وحشیactivator protein 1 - پروتئین فعال کننده 1mitogen-activated protein kinase - پروتئین کیناز فعال با mitogenChagas cardiomyopathy - کاردیومیوپاتی Chagas
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Cardiac dysfunction with progressive inflammation and fibrosis is a hallmark of Chagas disease caused by persistent Trypanosoma cruzi infection. Osteopontin (OPN) is a pro-inflammatory cytokine that orchestrates mechanisms controlling cell recruitment and cardiac architecture. Our main goal was to study the role of endogenous OPN as a modulator of myocardial CCL5 chemokine and MMP-2 metalloproteinase, and its pathological impact in a murine model of Chagas heart disease. Wild-type (WT) and OPN-deficient (spp1 â/â) mice were parasite-infected (Brazil strain) for 100Â days. Both groups developed chronic myocarditis with similar parasite burden and survival rates. However, spp1 â/â infection showed lower heart-to-body ratio (PÂ <Â 0.01) as well as reduced inflammatory pathology (PÂ <Â 0.05), CCL5 expression (PÂ <Â 0.05), myocyte size (PÂ <Â 0.05) and fibrosis (PÂ <Â 0.01) in cardiac tissues. Intense OPN labeling was observed in inflammatory cells recruited to infected heart (PÂ <Â 0.05). Plasma concentration of MMP-2 was higher (PÂ <Â 0.05) in infected WT than in spp1 â/â mice. Coincidently, specific immunostaining revealed increased gelatinase expression (PÂ <Â 0.01) and activity (PÂ <Â 0.05) in the inflamed hearts from T. cruzi WT mice, but not in their spp1 â/â littermates. CCL5 and MMP-2 induction occurred preferentially (PÂ <Â 0.01) in WT heart-invading CD8+ T cells and was mediated via phospho-JNK MAPK signaling. Heart levels of OPN, CCL5 and MMP-2 correlated (PÂ <Â 0.01) with collagen accumulation in the infected WT group only. Endogenous OPN emerges as a key player in the pathogenesis of chronic Chagas heart disease, through the upregulation of myocardial CCL5/MMP-2 expression and activities resulting in pro-inflammatory and pro-hypertrophic events, cardiac remodeling and interstitial fibrosis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1864, Issue 1, January 2018, Pages 11-23
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1864, Issue 1, January 2018, Pages 11-23
نویسندگان
Eugenia Pérez Caballero, Miguel H. SantamarÃa, Ricardo S. Corral,