Academic Journal
{alpha}11 integrin stimulates myofibroblast differentiation in diabetic cardiomyopathy
| العنوان: | {alpha}11 integrin stimulates myofibroblast differentiation in diabetic cardiomyopathy |
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| المؤلفون: | Talior-Volodarsky, Ilana, Connelly, Kim A., Arora, Pamma D., Gullberg, Donald, McCulloch, Christopher A. |
| بيانات النشر: | Oxford University Press |
| سنة النشر: | 2012 |
| المجموعة: | HighWire Press (Stanford University) |
| مصطلحات موضوعية: | Original Article |
| الوصف: | Aims Diabetic cardiomyopathy is characterized by the production of a disorganized fibrotic matrix in the absence of coronary atherosclerosis and hypertension. We examined whether adhesion of cardiac fibroblasts to glycated collagens mediates the differentiation of pro-fibrotic myofibroblasts, which may contribute to cardiac fibrosis. Methods and results By microarray, we found that methylglyoxal-treated collagen selectively enhanced α11 integrin expression in human cardiac fibroblasts, while levels of other collagen-binding integrins (α1, α2, and α10) were unchanged. Similar increases in α11 integrin mRNA and protein expression were observed in cardiac fibroblasts from streptozotocin (STZ)-treated Sprague–Dawley rats. In human cardiac fibroblasts plated on methyglyoxal-treated collagen and in cardiac fibroblasts from diabetic rats, transforming growth factor (TGF)-β2 but not TGF-β1 or TGF-β3 was increased compared with controls. Knock-down of α11 integrin and TGF-β receptors with small-interfering RNA blocked the increased expression of TGF-β2, α-smooth muscle actin (α-SMA), and α11 integrin that were induced in cells plated on methylglyoxal-treated collagen. Further, inhibition of Smad3 signalling blocked methylglyoxal-collagen up-regulation of α11 integrin and α-SMA expression. Rats with STZ-induced diabetes exhibited increased phosphorylation of Smad3 in cardiac tissues compared with control rats. Conclusion Interactions between α11 integrins and the Smad-dependent TGF-β2 signalling may contribute to the formation of pro-fibrotic myofibroblasts and the development of a fibrotic interstitium in diabetic cardiomyopathy. |
| نوع الوثيقة: | text |
| وصف الملف: | text/html |
| اللغة: | English |
| Relation: | http://cardiovascres.oxfordjournals.org/cgi/content/short/cvs259v2; http://dx.doi.org/10.1093/cvr/cvs259 |
| DOI: | 10.1093/cvr/cvs259 |
| الاتاحة: | http://cardiovascres.oxfordjournals.org/cgi/content/short/cvs259v2 https://doi.org/10.1093/cvr/cvs259 |
| Rights: | Copyright (C) 2012, European Society of Cardiology |
| رقم الانضمام: | edsbas.C5C917A |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/cvr/cvs259 |
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