首页> 外文期刊>American Journal of Physiology >Blockade of hypoxia-reoxygenation-mediated collagen type I expression and MMP activity by overexpression of TGF-beta1 delivered by AAV in mouse cardiomyocytes.
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Blockade of hypoxia-reoxygenation-mediated collagen type I expression and MMP activity by overexpression of TGF-beta1 delivered by AAV in mouse cardiomyocytes.

机译:AAV传递的TGF-beta1在小鼠心肌细胞中的过表达可阻止缺氧-复氧介导的I型胶原蛋白表达和MMP活性。

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Transforming growth factor (TGF)-beta(1) is one of the most pleiotropic and multifunctional peptides known. While the cardioprotective effect of TGF-beta(1) during ischemia is well known, the specific role of TGF-beta(1) in altering the cardiac remodeling process remains unclear. This study was designed to examine the regulation of hypoxia-reoxygenation-mediated collagen type I expression and activity of matrix metalloproteinases (MMPs) by overexpression of TGF-beta(1) in cultured HL-1 mouse cardiomyocytes. TGF-beta(1) was overexpressed in cardiomyocytes by transfection with adeno-associated virus (AAV)/TGF-beta(1)(Latent) or with AAV/TGF-beta(1)(ACT) (active TGF-beta(1)). Twenty-four hours of hypoxia followed by 3 h of reoxygenation (H-R) markedly enhanced (pro)collagen type I expression and activity of MMPs concomitant with an increase in reactive oxygen species (ROS) release and LOX-1 expression. Overexpression of TGF-beta(1) reduced these alterations induced by H-R. TGF-beta(1) overexpression also blocked H-R-mediated p38 and p44/42 MAPK activation. Transfection with AAV/TGF-beta(1)(ACT) was superior to that with AAV/TGF-beta(1)(Latent). These data for the first time demonstrate that H-R induces signals for cardiac remodeling in cardiomyocytes and TGF-beta(1) can modulate, possibly via antioxidant mechanism, these signals. These findings contribute to further understanding of the role of TGF-beta(1) in the cardiac remodeling process.
机译:转化生长因子(TGF)-β(1)是已知的多效性和多功能肽之一。虽然众所周知,TGF-β(1)在局部缺血期间具有心脏保护作用,但尚不清楚TGF-β(1)在改变心脏重塑过程中的具体作用。这项研究旨在检查在培养的HL-1小鼠心肌细胞中过表达TGF-beta(1)对缺氧-复氧介导的I型胶原蛋白表达和基质金属蛋白酶(MMPs)活性的调节。通过转染腺相关病毒(AAV)/ TGF-beta(1)(潜在)或AAV / TGF-beta(1)(ACT)(活性TGF-beta(1)在心肌细胞中过表达TGF-beta(1) ))。缺氧二十四小时,然后再充氧(H-R)3小时,显着增强了I型胶原(原)的表达和MMPs的活性,同时增加了活性氧(ROS)的释放和LOX-1的表达。 TGF-beta(1)的过表达减少了H-R诱导的这些改变。 TGF-beta(1)的过表达也阻止了H-R介导的p38和p44 / 42 MAPK激活。 AAV / TGF-beta(1)(ACT)的转染优于AAV / TGF-beta(1)(潜在)的转染。这些数据首次证明H-R在心肌细胞中诱导心脏重构的信号,而TGF-beta(1)可能通过抗氧化机制调节这些信号。这些发现有助于进一步了解TGF-beta(1)在心脏重塑过程中的作用。

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