کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8259804 | 1534645 | 2015 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Opposing roles of miR-21 and miR-29 in the progression of fibrosis in Duchenne muscular dystrophy
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کلمات کلیدی
Duchenne muscle dystrophyCOL6A1Collagen type I alpha 1YY1FBN1Col3a1COL1A1PAI-1ECMDMDERKHMGA2α-SMATGF-β1miRNAsα-smooth muscle actin - اکتین عضله آلفا صافmiR-21 - به miR-21miR-29 - به miR-29Transforming growth factor-β1 - تبدیل فاکتور رشد β1Duchenne muscular dystrophy - دیستروفی عضلانی دوشنmicroRNAs - ریز آرانایphosphatase and tensin homolog deleted on chromosome 10 - فسفاتاز و هومولوگ تنسین حذف شده در کروموزوم 10Fibroblast - فیبروبلاستFibrosis - فیبروز یا فساد الیافFibrillin 1 - فیبریلین 1Extracellular matrix - ماتریکس خارج سلولیMdx mouse - ماوس MdxPlasminogen activator inhibitor-1 - مهار کننده فعال کننده پلاسمینوژن-1Myoblast - میوبلاستPten - ژن PTENextracellular signal-regulated kinase - کیناز تنظیم شده سیگنال خارج سلولیYin Yang 1 - یین یانگ 1
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Excessive extracellular matrix deposition progressively replacing muscle fibres is the endpoint of most severe muscle diseases. Recent data indicate major involvement of microRNAs in regulating pro- and anti-fibrotic genes. To investigate the roles of miR-21 and miR-29 in muscle fibrosis in Duchenne muscle dystrophy, we evaluated their expression in muscle biopsies from 14 patients, and in muscle-derived fibroblasts and myoblasts. In Duchenne muscle biopsies, miR-21 expression was significantly increased, and correlated directly with COL1A1 and COL6A1 transcript levels. MiR-21 expression was also significantly increased in Duchenne fibroblasts, more so after TGF-β1 treatment. In Duchenne fibroblasts the expression of miR-21 target transcripts PTEN (phosphatase and tensin homolog deleted on chromosome 10) and SPRY-1 (Sprouty homolog 1) was significantly reduced; while collagen I and VI transcript levels and soluble collagen production were significantly increased. MiR-29a and miR-29c were significantly reduced in Duchenne muscle and myoblasts, and miR-29 target transcripts, COL3A1, FBN1 and YY1, significantly increased. MiR-21 silencing in mdx mice reduced fibrosis in the diaphragm muscle and in both Duchenne fibroblasts and mdx mice restored PTEN and SPRY-1 expression, and significantly reduced collagen I and VI expression; while miR-29 mimicking in Duchenne myoblasts significantly decreased miR-29 target transcripts. These findings indicate that miR-21 and miR-29 play opposing roles in Duchenne muscle fibrosis and suggest that pharmacological modulation of their expression has therapeutic potential for reducing fibrosis in this condition.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1852, Issue 7, July 2015, Pages 1451-1464
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1852, Issue 7, July 2015, Pages 1451-1464
نویسندگان
Simona Zanotti, Sara Gibertini, Maurizio Curcio, Paolo Savadori, Barbara Pasanisi, Lucia Morandi, Ferdinando Cornelio, Renato Mantegazza, Marina Mora,