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首页> 外文期刊>Journal of Cellular Physiology >Glycated Collagen Induces alpha 11 Inegrin Expression Through TGF-beta 2 and Smad3
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Glycated Collagen Induces alpha 11 Inegrin Expression Through TGF-beta 2 and Smad3

机译：11 Inegrin糖化胶原诱导α通过鉴定及2和Smad3表达式

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摘要

The adhesion of cardiac fibroblasts to the glycated collagen intarstitium in diabetics is associated with de novo expression of the a I I integrin, myofibroblast formation and cardiac fibrosis. We examined how methylglyoxal-glycated collagen regulates a I I integrin expression. In cardiac fibroblasts plated on glycated collagen but not glycated fibronectin, there was markedly increased a I 1 integrin and a-smooth muscle actin expression. Compared with native collagen, binding of purified a I I (3 I integrin to glycated collagen was reduced by >fourfold, which was consistent with reduced fibroblast attachment to glycated collagen. Glycated collagen strongly enhanced the expression of TGF-P2 but not TGF-p 1 or TGF-p3. The increased expression of TGF-(32 was inhibited by triple helical collagen peptides that mimic the a I I @ I integrin binding site on type I collagen. In cardiac fibroblasts transfected with a! I integrin luciferase promoter constructs, glycated collagen activated the a I I integrin promoter. Analysis of a! ! integrin promoter truncation mutants showed a novel Smad2/3 binding site located between —809 and — 1300 nt that was required for promoter activation. We conclude that glycated collagen in the cardiac interstitium triggers an autocrine TGF-(i2 signaling pathway that stimulates a ! I integrin expression through Smad2/3 binding elements in the cxt I integrin promoter, which is important for myofibroblast formation and fibrosis.
机译：心脏成纤维细胞的粘附胶原蛋白糖化intarstitium糖尿病患者与我新创的表达整合素,myofibroblast形成和心脏纤维化胶原蛋白调节我整合素表达。心脏成纤维细胞胶原蛋白糖化镀但不是糖化纤连蛋白,有明显增加了我1整合素和平滑的肌肉肌动蛋白的表达。绑定的净化我我(3整合素胶原蛋白糖化是减少>四倍,和成纤维细胞减少附件是一致的吗胶原蛋白糖化。增强TGF-P2但不是TGF-p 1的表达或TGF-p3。是由三重螺旋抑制胶原蛋白肽模仿我的我@整合素结合位点I型胶原蛋白。转染了!启动子结构,胶原蛋白糖化激活我整合蛋白启动子的我。整合素启动子截断突变体显示小说Smad2/3结合位点位于-809和所需的启动子- 1300元激活。心脏间质触发一个自分泌TGF - (i2信号通路,刺激!整合素通过Smad2/3绑定表达式元素cxt我整合素启动子,myofibroblast形成和重要纤维化

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