首页> 外文期刊>Cornea >Smad7 Suppresses the Inhibitory Effect of TGF-beta2 on Corneal Endothelial Cell Proliferation and Accelerates Corneal Endothelial Wound Closure In Vitro.
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Smad7 Suppresses the Inhibitory Effect of TGF-beta2 on Corneal Endothelial Cell Proliferation and Accelerates Corneal Endothelial Wound Closure In Vitro.

机译:Smad7抑制TGF-beta2对角膜内皮细胞增殖的抑制作用,并加速体外角膜内皮伤口闭合。

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PURPOSE The inhibitory activity of transforming growth factor-beta2 (TGF-beta2) on corneal endothelial cell proliferation is thought to be a cause of the limited regenerative capacity of corneal endothelial cells that may be related to impaired corneal transparency when many corneal endothelial cells are lost due to various stresses. We determined whether Smad7, an intracellular antagonist of TGF-beta signaling, regulated the inhibitory activity of TGF-beta2 or aqueous humor on corneal endothelial cell proliferation.METHODS The effect of Smad7 on TGF-beta2- or aqueous humor-mediated inhibition of corneal endothelial cell proliferation was evaluated using thymidine uptake assay with cultured rabbit corneal endothelial cells infected with adenovirus carrying Smad7. Expression of Smad or cell cycle-related proteins was detected by immunoblotting. In addition, a small scrape wound was made across a monolayer of Smad7-expressing cultured rabbit corneal endothelial cells to examine the effect of Smad7 on thewound-healing process in vitro.RESULTS Overexpression of Smad7 abolished the inhibitory effect of TGF-beta2 or aqueous humor on the proliferation of cultured rabbit corneal endothelial cells associated with the inhibition of phosphorylation of Smad2 and downregulation of p27kip1. Smad7-overexpressing cultured rabbit corneal endothelial cells exhibited shorter wound closure time in the presence of aqueous humor than LacZ-expressing cells.CONCLUSION Overexpression of Smad7 suppressed the inhibitory effect of TGF-beta2 or aqueous humor on corneal endothelial cell proliferation and accelerated corneal endothelial wound closure in vitro. Modification of Smad7 expression in corneal endothelial cells may thus have applicability in the treatment of wounded corneal endothelium.
机译:目的转化生长因子-β2(TGF-β2)对角膜内皮细胞增殖的抑制活性被认为是角膜内皮细胞再生能力有限的原因,这可能与失去许多角膜内皮细胞时角膜透明性受损有关。由于各种压力。我们确定了Smad7(一种TGF-β信号转导的细胞内拮抗剂)是否调节了TGF-β2或房水对角膜内皮细胞增殖的抑制活性。方法Smad7对TGF-β2或房水介导的角膜内皮细胞抑制作用使用胸腺嘧啶核苷摄取测定法,用感染了携带Smad7的腺病毒的兔角膜内皮细胞进行培养,评估细胞的增殖。通过免疫印迹检测Smad或细胞周期相关蛋白的表达。此外,在表达Smad7的培养兔角膜内皮细胞的单层上划了一个小刮伤,以检查Smad7对体外伤口愈合过程的影响。结果Smad7的过表达消除了TGF-beta2或房水的抑制作用。对培养的兔角膜内皮细胞增殖的抑制作用与抑制Smad2的磷酸化和下调p27kip1有关。结论:Smad7过表达培养的兔角膜内皮细胞在房水存在下的伤口闭合时间比LacZ表达细胞短。体外封闭。因此,角膜内皮细胞中Smad7表达的修饰可能在治疗受伤的角膜内皮中具有适用性。

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