Microphthalmia-associated Transcription Factor (MITF) Promotes Differentiation of Human Retinal Pigment Epithelium (RPE) by Regulating microRNAs-204/211 Expression

被引:98
作者
Adijanto, Jeffrey [1 ]
Castorino, John J. [1 ]
Wang, Zi-Xuan [1 ]
Maminishkis, Arvydas [2 ]
Grunwald, Gerald B. [1 ]
Philp, Nancy J. [1 ]
机构
[1] Thomas Jefferson Univ, Dept Anat Pathol & Cell Biol, Philadelphia, PA 19107 USA
[2] NEI, NIH, Bethesda, MD 20892 USA
基金
美国国家卫生研究院;
关键词
MESENCHYMAL TRANSITION; GENE-THERAPY; CONGENITAL AMAUROSIS; MICRORNA EXPRESSION; MIR-200; FAMILY; CELL FATE; LET-7; GROWTH; HMGA2; IDENTIFICATION;
D O I
10.1074/jbc.M112.354761
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The retinal pigment epithelium (RPE) plays a fundamental role in maintaining visual function and dedifferentiation of RPE contributes to the pathophysiology of several 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 down-regulated 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 down-regulated in dedifferentiated hfRPE cells. MITF knockdown decreased miR-204/211 expression and caused hfRPE dedifferentiation. Significantly, co-transfection of MITF siRNA with pre-miR-204/211 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 dedifferentiation such as proliferative vitreoretinopathy.
引用
收藏
页码:20491 / 20503
页数:13
相关论文
共 57 条
[1]   CO2-induced ion and fluid transport in human retinal pigment epithelium [J].
Adijanto, Jeffrey ;
Banzon, Tina ;
Jalickee, Stephen ;
Wang, Nam S. ;
Miller, Sheldon S. .
JOURNAL OF GENERAL PHYSIOLOGY, 2009, 133 (06) :603-622
[2]   The impact of microRNAs on protein output [J].
Baek, Daehyun ;
Villen, Judit ;
Shin, Chanseok ;
Camargo, Fernando D. ;
Gygi, Steven P. ;
Bartel, David P. .
NATURE, 2008, 455 (7209) :64-U38
[3]   Effect of gene therapy on visual function in Leber's congenital amaurosis [J].
Bainbridge, James W. B. ;
Smith, Alexander J. ;
Barker, Susie S. ;
Robbie, Scott ;
Henderson, Robert ;
Balaggan, Kamaljit ;
Viswanathan, Ananth ;
Holder, Graham E. ;
Stockman, Andrew ;
Tyler, Nick ;
Petersen-Jones, Simon ;
Bhattacharya, Shomi S. ;
Thrasher, Adrian J. ;
Fitzke, Fred W. ;
Carter, Barrie J. ;
Rubin, Gary S. ;
Moore, Anthony T. ;
Ali, Robin R. .
NEW ENGLAND JOURNAL OF MEDICINE, 2008, 358 (21) :2231-2239
[4]   MicroRNAs: Target Recognition and Regulatory Functions [J].
Bartel, David P. .
CELL, 2009, 136 (02) :215-233
[5]  
Bumsted KM, 2000, INVEST OPHTH VIS SCI, V41, P903
[6]   Fifteen-year quest for microphthalmia-associated transcription factor target genes [J].
Cheli, Yann ;
Ohanna, Mickael ;
Ballotti, Robert ;
Bertolotto, Corine .
PIGMENT CELL & MELANOMA RESEARCH, 2010, 23 (01) :27-40
[7]   MicroRNAs modulate hematopoietic lineage differentiation [J].
Chen, CZ ;
Li, L ;
Lodish, HF ;
Bartel, DP .
SCIENCE, 2004, 303 (5654) :83-86
[8]   miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche [J].
Cheng, Li-Chun ;
Pastrana, Erika ;
Tavazoie, Masoud ;
Doetsch, Fiona .
NATURE NEUROSCIENCE, 2009, 12 (04) :399-408
[9]   MicroRNA-145, a Novel Smooth Muscle Cell Phenotypic Marker and Modulator, Controls Vascular Neointimal Lesion Formation [J].
Cheng, Yunhui ;
Liu, Xiaojun ;
Yang, Jian ;
Lin, Ying ;
Xu, Da-Zhong ;
Lu, Qi ;
Deitch, Edwin A. ;
Huo, Yuqing ;
Delphin, Ellise S. ;
Zhang, Chunxiang .
CIRCULATION RESEARCH, 2009, 105 (02) :158-U113
[10]   Human RPE65 Gene Therapy for Leber Congenital Amaurosis: Persistence of Early Visual Improvements and Safety at 1 Year [J].
Cideciyan, Artur V. ;
Hauswirth, William W. ;
Aleman, Tomas S. ;
Kaushal, Shalesh ;
Schwartz, Sharon B. ;
Boye, Sanford L. ;
Windsor, Elizabeth A. M. ;
Conlon, Thomas J. ;
Sumaroka, Alexander ;
Pang, Ji-jing ;
Roman, Alejandro J. ;
Byrne, Barry J. ;
Jacobson, Samuel G. .
HUMAN GENE THERAPY, 2009, 20 (09) :999-1004