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实验性诱导近视豚鼠模型巩膜成纤维细胞中Wnt/β-连环蛋白信号通路的表达及其对I型胶原蛋白与转化生长因子-β1的调控作用

Expression of Wnt/β-Catenin Signaling Pathway and Its Regulatory Role in Type I Collagen with TGF-β1 in Scleral Fibroblasts from an Experimentally Induced Myopia Guinea Pig Model.

作者信息

Li Min, Yuan Ying, Chen Qingzhong, Me Rao, Gu Qing, Yu Yunjie, Sheng Minjie, Ke Bilian

机构信息

Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of Ophthalmology, Yangpu Hospital, Tongji University, Shanghai, China.

出版信息

J Ophthalmol. 2016;2016:5126560. doi: 10.1155/2016/5126560. Epub 2016 May 10.

Abstract

Background. To investigate Wnt/β-catenin signaling pathway expression and its regulation of type I collagen by TGF-β1 in scleral fibroblasts from form-deprivation myopia (FDM) guinea pig model. Methods. Wnt isoforms were examined using genome microarrays. Scleral fibroblasts from FDM group and self-control (SC) group were cultured. Wnt isoforms, β-catenin, TGF-β1, and type I collagen expression levels were examined in the two groups with or without DKK-1 or TGF-β1 neutralizing antibody. Results. For genome microarrays, the expression of Wnt3 in FDM group was significantly greater as confirmed in retinal and scleral tissue. The expression of Wnt3 and β-catenin significantly increased in FDM group and decreased significantly with DKK-1. TGF-β1 expression level decreased significantly in FDM group and increased significantly with DKK-1. Along with morphological misalignment inside and outside cells, the amount of type I collagen decreased in FDM group. Furthermore, type I collagen increased and became regular in DKK-1 intervention group, whereas it decreased and rearranged more disorder in TGF-β1 neutralizing antibody intervention group. Conclusions. The activation of Wnt3/β-catenin signaling pathway was demonstrated in primary scleral fibroblasts in FDM. This pathway further reduced the expression of type I collagen by TGF-β1, which ultimately played a role in scleral remodeling during myopia development.

摘要

背景。研究形觉剥夺性近视(FDM)豚鼠模型巩膜成纤维细胞中Wnt/β-连环蛋白信号通路的表达及其受转化生长因子-β1(TGF-β1)对I型胶原蛋白的调控。方法。使用基因组微阵列检测Wnt亚型。培养FDM组和自身对照(SC)组的巩膜成纤维细胞。在有或没有DKK-1或TGF-β1中和抗体的情况下,检测两组中Wnt亚型、β-连环蛋白、TGF-β1和I型胶原蛋白的表达水平。结果。对于基因组微阵列,视网膜和巩膜组织证实FDM组中Wnt3的表达显著更高。FDM组中Wnt3和β-连环蛋白的表达显著增加,而用DKK-1处理后显著降低。FDM组中TGF-β1表达水平显著降低,用DKK-1处理后显著增加。随着细胞内外形态排列紊乱,FDM组中I型胶原蛋白的量减少。此外,DKK-1干预组中I型胶原蛋白增加且变得规则,而TGF-β1中和抗体干预组中其减少且排列更紊乱。结论。在FDM的原代巩膜成纤维细胞中证实了Wnt3/β-连环蛋白信号通路的激活。该通路进一步降低了TGF-β1对I型胶原蛋白的表达,这最终在近视发展过程中的巩膜重塑中起作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e7d/4877496/c175a57680d9/JOPH2016-5126560.001.jpg

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