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培养的视网膜色素上皮(RPE)细胞的上皮-间质转化

Epitheliomesenchymal transdifferentiation of cultured RPE cells.

作者信息

Lee S C, Kwon O W, Seong G J, Kim S H, Ahn J E, Kay E D

机构信息

Department of Ophthalmology and Institute of Vision Research, Yonsei University College of Medicine, Seoul, Korea.

出版信息

Ophthalmic Res. 2001 Mar-Apr;33(2):80-6. doi: 10.1159/000055648.

DOI:10.1159/000055648
PMID:11244352
Abstract

Retinal pigment epithelium (RPE) cells of the proliferative vitreoretinopathy (PVR) membrane take on the shape of fibroblasts and participate in fibrosis, thus deviating from the character of epithelial cells. This study was undertaken to evaluate RPE cell transdifferentiation in vitro. During the culture of porcine RPE cells, primary and 10th-passaged RPE cells were investigated for cell growth in response to transforming growth factor (TGF) beta(2), change of phenotype and amount in collagen synthesis as well as expression of alpha-smooth-muscle actin (alpha-SMA). TGF-beta(2) inhibited the proliferation of the primary cultures of RPE cells in a dose-dependent manner, while the spindle-shaped 10th-passaged RPE cells were not inhibited by TGF-beta(2). The 10th-subcultured cells did not show much difference in the quality of collagen synthesis, other than type VIII collagen which was not produced. Collagen synthesis was dose-dependently stimulated by TGF-beta(2). The stimulation by TGF-beta(2) in the 10th-passaged RPE cells was much greater than in primary RPE cells. The 10th-subcultured RPE cells produced substantial alpha-SMA compared to alpha-SMA production by primary RPE cells. These results were also observed by confocal laser microscopy. These findings indicated that RPE metaplasia resulting in a change of biological cell behavior might be a necessary predisposing step in the development of PVR.

摘要

增殖性玻璃体视网膜病变(PVR)膜中的视网膜色素上皮(RPE)细胞呈现成纤维细胞形态并参与纤维化过程,从而背离了上皮细胞的特性。本研究旨在评估RPE细胞在体外的转分化情况。在猪RPE细胞培养过程中,对原代和传代10次的RPE细胞进行了研究,观察它们对转化生长因子(TGF)β2的细胞生长反应、表型变化、胶原蛋白合成量以及α平滑肌肌动蛋白(α-SMA)的表达。TGF-β2以剂量依赖方式抑制原代培养的RPE细胞增殖,而呈纺锤形的传代10次的RPE细胞不受TGF-β2抑制。传代10次的细胞在胶原蛋白合成质量上没有太大差异,但不产生VIII型胶原蛋白。TGF-β2能剂量依赖性地刺激胶原蛋白合成。TGF-β2对传代10次的RPE细胞的刺激作用远大于原代RPE细胞。与原代RPE细胞产生的α-SMA相比,传代10次的RPE细胞产生了大量的α-SMA。共聚焦激光显微镜也观察到了这些结果。这些发现表明,导致生物细胞行为改变的RPE化生可能是PVR发生发展过程中一个必要的前期步骤。

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