Mertk deficiency alters expression of micrornas in the retinal pigment epithelium cells
| Autor: | Qingjun Lu, Qingxian Lu, Yunrong Wei, Qiutang Li, Lixia Han, Rui Ji, Yong Tang |
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| Rok vydání: | 2015 |
| Předmět: |
Retinal degeneration
Retinal Pigment Epithelium Biology C-Mer Tyrosine Kinase Biochemistry Article Mice Cellular and Molecular Neuroscience Proto-Oncogene Proteins microRNA Myosin medicine Animals Gene Cells Cultured Mice Knockout Genetics Regulation of gene expression Retinal pigment epithelium c-Mer Tyrosine Kinase Receptor Protein-Tyrosine Kinases MERTK medicine.disease Cell biology MicroRNAs medicine.anatomical_structure Gene Expression Regulation Neurology (clinical) |
| Zdroj: | Metabolic Brain Disease. 30:943-950 |
| ISSN: | 1573-7365 0885-7490 |
| DOI: | 10.1007/s11011-015-9653-5 |
| Popis: | Phagocytic clearance of the spent photoreceptor outer segments (OS) by RPE cells is regulated by circadian rhythm cycle and is essential for photoreceptor integrity and function. Mertk regulates RPE phagocytosis and a deficiency in Mertk causes photoreceptor degeneration and visual loss. This study aimed to investigate Mertk regulation of the microRNAs (miRNA), potentially regulating expression of their target genes, which affect phagocytosis. The differentially expressed miRNAs were identified using miRCURY™ microRNA Arrays from total RNA isolated at 0900hr and 1900hr from the mechanically dissociated RPE sheets of the WT and Mertk−/− mice, which were housed in a 12-hour light-dark cycle with the lighting onset at 0700hr (7:00am). Validation of the differentially expressed miRNAs and assessment of the putative miRNA target gene expression were performed by real-time PCR. Among the differentially expressed miRNAs in the Mertk−/− RPE, seven miRNAs were up-regulated and thirteen were down-regulated in the morning groups. Similarly, twenty four miRNAs were found to be up-regulated and thirteen were down-regulated in the evening groups. To search for those that may participate in regulating expression of cytoskeletal proteins, we examined the predicted target genes that might participate in phagocytosis were examined by real-time PCR. Of nine potential altered targets, four deregulated genes were myosin subunits. Notably, multiple members of the 21 up-regulated miRNAs can theoretically recognize these down-regulated mRNAs, particularly MyH14 and Myl3. This study shows that loss of Mertk alters miRNA expression, which in turn affects expression of the downstream target genes, potentially affecting phagocytosis. |
| Databáze: | OpenAIRE |
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