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JBC:发现促进人类视网膜色素上皮细胞分化的miRNAs

来源:生物谷 2012-04-21 16:59

视网膜色素上皮细胞(RPE)与视觉功能的维持息息相关,而RPE的去分化会导致几种增生性眼部疾病。

为了鉴定与RPE分化有关的microRNAs (miRNAs),近日托马斯杰弗逊大学的研究人员比较了已分化的初级人类胚胎RPE(hfRPE)细胞与去分化的hfRPE细胞的miRNA表达图谱。

研究发现,miR-204/211是RPE中两种高表达的miRNAs,它们在去分化的hfRPE细胞中被显著下调。

重要的是,把pre-miR-204/211转染进hfRPE细胞会促进RPE分化,而加入miR-204/211抑制剂后会导致它们的去分化。

小眼畸形有关转录因子(MITF)是RPE分化一个主要的调节因子,它在去分化的hfRPE细胞中被下调。MITF的敲除会减少miR-204/211的表达,并引起hfRPE去分化。

值得注意的是,联合转染MITF siRNA与miR-204/211能够恢复RPE表型。

总的说来,这些数据表明miR-204/211能够促进RPE分化,那么miR-204/211很可能会成为与RPE去分化有关疾病(比如增生性玻璃体视网膜病变)的治疗靶点。相关论文发表在4月20日的The Journal of Biological Chemistry。(生物谷Deepblue编译)

Microphthalmia-associated transcription factor (MITF) promotes differentiation of human retinal pigment epithelium (RPE) by regulating microRNA-204/211 expression

Jeffrey Adijanto, John J. Castorino, Zi-Xuan Wang, Arvydas Maminishkis, Gerald B. Grunwald and Nancy J. Philp.

The retinal pigment epithelium (RPE) plays a fundamental role in maintaining visual function and dedifferentiation of RPE contributes to the pathophysiology of several proliferative ocular diseases.To identify microRNAs (miRNAs) that may be involved in RPE differentiation, we compared the miRNA expression profiles of differentiated primary human fetal RPE (hfRPE) cells to dedifferentiated hfRPE cells. We found that miR-204/211, the two most highly expressed miRNAs in the RPE, were significantly downregulated in dedifferentiated hfRPE cells.Importantly, transfection of pre-miR-204/211 into hfRPE cells promoted differentiation whereas adding miR-204/211 inhibitors led to their dedifferentiation.Microphthalmia-associated transcription factor (MITF) is a key regulator of RPE differentiation that was also downregulated in dedifferentiated hfRPE cells.MITF-knockdown decreased miR-204/211 expression and caused hfRPE dedifferentiation. Significantly, co-transfection of MITF siRNA with miR-204/211 mimics rescued RPE phenotype. Collectively, our data show that miR-204/211 promote RPE differentiation, suggesting that miR-204/211-based therapeutics may be effective treatments for diseases that involve RPE dedifferentation such as proliferative vitreoretinopathy.

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