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首页> 外文期刊>The ocular surface >Moesin as a key cytoskeleton regulator in corneal fibrosis
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Moesin as a key cytoskeleton regulator in corneal fibrosis

机译：Moesin是角膜纤维化的关键细胞骨架调节剂

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Purpose: Corneal fibrosis is the third leading cause of blindness worldwide. α-Smooth muscle actin (SMA), a marker of fibrosis, is closely regulated through an intermediate group of submembrane molecules e cytoskeleton regulators. The purpose of this study was to elucidate the role of specific cytoskeleton regulators in amousemodel of corneal fibrosis. Methods: A mouse model of corneal fibrosis was developed using anterior keratectomy (AK) and the topical application of transforming growth factor (TGF)-β1 (1 μg/ml). The RT2 ProfilerTM PCR Array for cytoskeleton regulators was used to assay changes in levels of specific members of this class of proteins. Moesin siRNA was delivered into the corneal stroma by iontophoresis in vivo. Transformation of the corneal keratocyte-to-myofibroblast in corneal fibrosis, as defined by the expression of α-SMA, was determined by Western blot. Results: After AK and topical application of TGF-β1, moesin was the most highly upregulated gene among 84 cytoskeleton regulator genes; iontophoresing moesin siRNA into the corneal stroma reduced the expression of α-SMA to 0.22-, 0.52-, and 0.31-fold of control at postoperative (PO) day 1, 3, and 5, respectively; also, upregulation of phospho-Smad 2 induced by TGF-β1 was reduced by moesin siRNA to 0.59-, 0.56-, and 0.31-fold of control and expression of phospho-Smad 3 was reduced to 0.58-, 0.53-, and 0.47-fold of control at the same PO days. Conclusions: Moesin may be a potential drug target for inhibiting corneal fibrosis, and the details of moesin-related signaling pathways would be critical for understanding corneal fibrosis.
机译：目的：角膜纤维化是全世界失明的第三大主要原因。 α-平滑肌肌动蛋白（SMA）是纤维化的标志物，通过亚膜分子的中间组和细胞骨架调节剂受到密切调节。这项研究的目的是阐明特定的细胞骨架调节剂在角膜纤维化的模型中的作用。方法：使用前角膜切除术（AK）和局部应用转化生长因子（TGF）-β1（1μg/ ml）建立了角膜纤维化小鼠模型。用于细胞骨架调节剂的RT2 ProfilerTM PCR阵列用于分析此类蛋白质特定成员水平的变化。 Moesin siRNA在体内通过离子电渗疗法传递到角膜基质中。通过Western印迹确定由α-SMA的表达所定义的角膜纤维化中角膜角膜细胞向成肌纤维细胞的转化。结果：经过AK和局部施用TGF-β1后，在84个细胞骨架调节基因中，moesin是上调程度最高的基因。在角膜基质中采用离子电渗疗法将moesin siRNA分别在术后第1、3和5天将α-SMA的表达分别降低至对照的0.22、0.52和0.31倍;另外，moesin siRNA将TGF-β1诱导的磷酸Smad 2的上调降低到对照的0.59-，0.56-和0.31倍，磷酸Smad 3的表达降低到0.58-，0.53-和0.47-。同一PO天的对照倍数。结论：肌动蛋白可能是抑制角膜纤维化的潜在药物靶标，与肌动蛋白有关的信号通路的详细信息对于理解角膜纤维化至关重要。

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