PMID:22523078

Citation	Adijanto, J, Castorino, JJ, Wang, ZX, Maminishkis, A, Grunwald, GB and Philp, NJ (2012) Microphthalmia-associated transcription factor (MITF) promotes differentiation of human retinal pigment epithelium (RPE) by regulating microRNAs-204/211 expression. J. Biol. Chem. 287:20491-503
Abstract	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.
Links	PubMed PMC3370234 Online version:10.1074/jbc.M112.354761
Keywords	Cell Differentiation/physiology; Cells, Cultured; Down-Regulation/physiology; Gene Knockdown Techniques; Humans; MicroRNAs/biosynthesis; MicroRNAs/genetics; Microphthalmia-Associated Transcription Factor/genetics; Microphthalmia-Associated Transcription Factor/metabolism; Retinal Pigment Epithelium/cytology; Retinal Pigment Epithelium/metabolism; Vitreoretinopathy, Proliferative/genetics; Vitreoretinopathy, Proliferative/metabolism; Vitreoretinopathy, Proliferative/therapy
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:MITF	involved_in	GO:0010628: positive regulation of gene expression	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:MITF		GO:0010628: positive regulation of gene expression	ECO:0000315:		P		Human fetal cells were transfected with MITF siRNA versus control siRNA. Figure 4B shows that a knockdown (reduction) of MITF causes a down-reguation of the gene TRPM1 when all other factors are held constant. Therefore, MITF is responsible for the upregulation of TRPM1.	complete CACAO 9965

References

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