کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10802212 | 1055668 | 2014 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A-kinase anchoring protein-Lbc promotes pro-fibrotic signaling in cardiac fibroblasts
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کلمات کلیدی
AVFmyocardin related transcription factorTGF-βNVMMRTFAKAPGEFECMRhoAGTPα-SMAAngiotensin II - آنژیوتانسین دوα-smooth muscle actin - اکتین عضله آلفا صافTransforming growth factor β - تبدیل فاکتور رشد βAng II - دومguanine nucleotide exchange factor - فاکتور تبادل نوکلئوتید گوانینCardiac fibroblast - فیبروبلاست قلبExtracellular matrix - ماتریکس خارج سلولیshort hairpin - موی سر کوتاهA-kinase anchoring protein - پروتئین anchoring A-kinaseprotein kinase A - پروتئین کیناز AGuanosine triphosphate - گوانوزین تری فسفاتα1-Adrenergic receptors - گیرنده های α1-adrenergicG protein-coupled receptor - گیرندههای جفتشونده با پروتئین جی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
In response to stress or injury the heart undergoes an adverse remodeling process associated with cardiomyocyte hypertrophy and fibrosis. Transformation of cardiac fibroblasts to myofibroblasts is a crucial event initiating the fibrotic process. Cardiac myofibroblasts invade the myocardium and secrete excess amounts of extracellular matrix proteins, which cause myocardial stiffening, cardiac dysfunctions and progression to heart failure. While several studies indicate that the small GTPase RhoA can promote profibrotic responses, the exchange factors that modulate its activity in cardiac fibroblasts are yet to be identified. In the present study, we show that AKAP-Lbc, an A-kinase anchoring protein (AKAP) with an intrinsic Rho-specific guanine nucleotide exchange factor (GEF) activity, is critical for activating RhoA and transducing profibrotic signals downstream of type I angiotensin II receptors (AT1Rs) in cardiac fibroblasts. In particular, our results indicate that suppression of AKAP-Lbc expression by infecting adult rat ventricular fibroblasts with lentiviruses encoding AKAP-Lbc specific short hairpin (sh) RNAs strongly reduces the ability of angiotensin II to promote RhoA activation, differentiation of cardiac fibroblasts to myofibroblasts, collagen deposition as well as myofibroblast migration. Interestingly, AT1Rs promote AKAP-Lbc activation via a pathway that requires the α subunit of the heterotrimeric G protein G12. These findings identify AKAP-Lbc as a key Rho-guanine nucleotide exchange factor modulating profibrotic responses in cardiac fibroblasts.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1843, Issue 2, February 2014, Pages 335-345
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1843, Issue 2, February 2014, Pages 335-345
نویسندگان
Sabrina Cavin, Darko Maric, Dario Diviani,