کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8473126 | 1550384 | 2018 | 56 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
TRAF3IP2 mediates TWEAK/TWEAKR-induced pro-fibrotic responses in cultured cardiac fibroblasts and the heart
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کلمات کلیدی
HLHCCLAct1ICAM1IKKinhibitory kappa BLVIDsAP-1IκBLVPWdCXCLCIKSiNOSCTGFgp130Fn14ECMC-C motif chemokine ligandDMEMJnkCT1ITSC-X-C motif chemokine ligandANPeGFPLVPWsGAPDHc-Jun N-terminal kinase - C-Jun N-terminal kinaseDMSO - DMSODulbecco's modified Eagle Medium - Eagle Medium اصلاح شده DulbeccoIκB kinase - IkB kinaseenzyme linked immunosorbent assay - آنزیم تست ایمونوسیورسانس مرتبط استinterleukin - اینترلوکینleft ventricle/left ventricular - بطن چپ / بطن چپELISA - تست الیزاcluster of differentiation - خوشه تمایزDimethyl sulfoxide - دیمتیل سولفواکسیدinducible nitric oxide synthase - سنتاز اکسید نیتریک القاییhelix-loop-helix - سیلیکون حلقه ایIntramuscular - عضلانیConnective tissue growth factor - فاکتور رشد بافت همبندcardiac fibroblasts - فیبروبلاست های قلبExtracellular matrix - ماتریکس خارج سلولیMigration - مهاجرتIntercellular adhesion molecule 1 - مولکول چسبندگی بین سلولی 1knockout - ناکاوتactivator protein-1 - پروتئین فعال کننده-1enhanced green fluorescent protein - پروتئین فلورسنت سبز افزایش یافته استatrial natriuretic peptide - پپتید نایروئیدوری دهلیزcardiotrophin 1 - کاردیوتروفین 1ejection fraction - کسری خروجیglyceraldehyde 3-phosphate dehydrogenase - گلیسرولیدید 3-فسفات دهیدروژنازglycoprotein 130 - گلیکوپروتئین 130
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
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چکیده انگلیسی
Persistent inflammation promotes development and progression of heart failure (HF). TWEAK (TNF-Related WEAK Inducer Of Apoptosis), a NF-κB- and/or AP-1-responsive proinflammatory cytokine that signals via TWEAK receptor (TWEAKR), is expressed at high levels in human and preclinical models of HF. Since the adapter molecule TRAF3IP2 (TRAF3 Interacting Protein 2) is an upstream regulator of various proinflammatory pathways, including those activated by NF-κB and AP-1, we hypothesized that targeting TRAF3IP2 inhibits TWEAK-induced proinflammatory and pro-fibrotic responses in vitro and in vivo. Consistent with the hypothesis, forced expression of TRAF3IP2 upregulated TWEAK and its receptor expression in cultured adult mouse cardiac fibroblasts (CF). Further, exogenous TWEAK upregulated TRAF3IP2 expression in a time- and dose-dependent manner, suggesting a positive-feedback regulation of TRAF3IP2 and TWEAK. TWEAK also promoted TRAF3IP2 nuclear translocation. Confirming its critical role in TWEAK signaling, silencing TRAF3IP2 inhibited TWEAK autoregulation, TWEAKR upregulation, p38 MAPK, NF-κB and AP-1 activation, inflammatory cytokine expression, MMP and TIMP1 activation, collagen expression and secretion, and importantly, proliferation and migration. Recapitulating these in vitro results, continuous infusion of TWEAK for 7â¯days increased systolic blood pressure (SBP), upregulated TRAF3IP2 expression, activated p38 MAPK, NF-κB and AP-1, induced the expression of multiple proinflammatory and pro-fibrotic mediators, and interstitial fibrosis in hearts of wild type mice. These proinflammatory and pro-fibrotic changes occurred in conjunction with myocardial hypertrophy and contractile dysfunction. Importantly, genetic ablation of TRAF3IP2 inhibited these TWEAK-induced adverse cardiac changes independent of increases in SBP, indicating that TRAF3IP2 plays a causal role, and thus a therapeutic target, in chronic inflammatory and fibro-proliferative diseases.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 121, August 2018, Pages 107-123
Journal: Journal of Molecular and Cellular Cardiology - Volume 121, August 2018, Pages 107-123
نویسندگان
Nitin A. Das, Andrea J. Carpenter, Tadashi Yoshida, Senthil A. Kumar, Sandeep Gautam, Ricardo Mostany, Reza Izadpanah, Ashok Kumar, Srinivas Mummidi, Ulrich Siebenlist, Bysani Chandrasekar,