Mertk deficiency alters expression of micrornas in the retinal pigment epithelium cells
Open accessAbstract
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(TM) microRNA Arrays from total RNA isolated at 0900 h and 1900 h from the mechanically dissociated RPE sheets of the WT and Mertk (-/-) mice, which were housed in a 12-h light-dark cycle with the lighting onset at 0700 h (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 13 were down-regulated in the morning groups. Similarly, 24 miRNAs were found to be up-regulated and 13 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.
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In Mertk knockout mice, Tang et al. identified deregulated microRNAs that putatively target genes involved in cytoskeletal regulation.
“They identified deregulated microRNAs that putatively target genes involved in cytoskeletal regulation; however, functional studies are lacking [275].”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [275]
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MicroRNAs as Regulators of Phagocytosis
Gierlikowski, W., & Gierlikowska, B. (2022) · Cells · doi:10.3390/cells11091380 · Cited by 25 · see citing works
- Authors
- Tang, Y., Lu, Q., Wei, Y., Han, L., Ji, R., Li, Q., & Lu, Q.
- Affiliations
- Capital Medical University (CN)
- Beijing Tongren Hospital (CN)
- University of Louisville (US)
- ORCID
- Venue
- Metabolic Brain Disease
- Published
- 2015-01-22
- Volume
- 30
- Issue
- 4
- Pages
- 943-950
- ISSN
- 0885-7490 (ISSN-L)
- 1573-7365
- PMC
- PMC4492868
- OpenAlex
- W1978919418
- Cited by
- 7
- References
- 6
- Citations by year
- 2025: 1 · 2022: 2 · 2021: 2 · 2017: 1 · 2016: 1
- FWCI
- 0.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Metabolic Brain Disease (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Research to Prevent Blindness
- National Institutes of Health
- National Eye Institute (R01EY018830)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- MERTK, retinal pigment epithelium, microRNA expression, phagocytosis, circadian rhythm, photoreceptor degeneration, MYH14, MYL3, cytoskeletal proteins, miRNA target genes
- MeSH terms
- c-Mer Tyrosine Kinase, Animals, Cells, Cultured, Gene Expression Regulation, Proto-Oncogene Proteins, Mice, Knockout, Receptor Protein-Tyrosine Kinases, MicroRNAs, Mice, Retinal Pigment Epithelium
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