دورية أكاديمية
miR-184 regulates ezrin, LAMP-1 expression, affects phagocytosis in human retinal pigment epithelium and is downregulated in age-related macular degeneration.
| العنوان: | miR-184 regulates ezrin, LAMP-1 expression, affects phagocytosis in human retinal pigment epithelium and is downregulated in age-related macular degeneration. |
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| المؤلفون: | Murad N; Department of Biochemistry and Molecular and Cellular Biology, Georgetown University Medical Center, Washington, DC, USA., Kokkinaki M, Gunawardena N, Gunawan MS, Hathout Y, Janczura KJ, Theos AC, Golestaneh N |
| المصدر: | The FEBS journal [FEBS J] 2014 Dec; Vol. 281 (23), pp. 5251-64. Date of Electronic Publication: 2014 Oct 13. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Published by Blackwell Pub. on behalf of the Federation of European Biochemical Societies Country of Publication: England NLM ID: 101229646 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1742-4658 (Electronic) Linking ISSN: 1742464X NLM ISO Abbreviation: FEBS J Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Oxford, UK : Published by Blackwell Pub. on behalf of the Federation of European Biochemical Societies, c2005- |
| مواضيع طبية MeSH: | Phagocytosis*, Cytoskeletal Proteins/*physiology , Lysosomal Membrane Proteins/*physiology , Macular Degeneration/*etiology , MicroRNAs/*physiology , Retinal Pigment Epithelium/*metabolism, Adolescent ; Aged ; Aged, 80 and over ; Cells, Cultured ; Child ; Cytoskeletal Proteins/genetics ; Down-Regulation ; Female ; Humans ; Lysosomal Membrane Proteins/genetics ; Macular Degeneration/genetics ; Macular Degeneration/metabolism ; Male ; Middle Aged ; Retinal Photoreceptor Cell Outer Segment/metabolism |
| مستخلص: | MicroRNA 184 (miR-184) is known to play a key role in neurological development and apoptosis and is highly expressed in mouse brain, mouse corneal epithelium, zebrafish lens and human retinal pigment epithelium (RPE). However, the role of miR-184 in RPE is largely unknown. We investigated the role of miR-184 in RPE and its possible implication in age-related macular degeneration (AMD). Proteomic analysis identified the ezrin (EZR) gene as a target of miR-184 in human RPE. EZR is a membrane cytoskeleton crosslinker that is also known to bind to lysosomal-associated membrane protein 1 (LAMP-1) during the formation of phagocytic vacuoles. In adult retinal pigment epithelium 19 (ARPE19) cells, inhibition of miR-184 resulted in upregulation of EZR mRNA and EZR protein, and induced downregulation of LAMP-1. The inhibition of miR-184 decreased EZR-bound LAMP-1 protein levels and affected phagocytic activity in ARPE19 cells. In primary culture of human RPE isolated from eyes of AMD donors (AMD RPE), miR-184 was significantly downregulated compared with control (normal) RPE. Downregulation of miR-184 was consistent with significantly lower levels of LAMP-1 protein in AMD RPE, and overexpression of MIR-184 in AMD RPE was able to rescue LAMP-1 protein expression to normal levels. Altogether, these observations suggest a novel role for miR-184 in RPE health and support a model proposing that downregulation of miR-184 expression during aging may result in dysregulation of RPE function, contributing to retinal degeneration. (© 2014 FEBS.) |
| فهرسة مساهمة: | Keywords: AMD; LAMP-1; RPE; ezrin; miR-184 |
| المشرفين على المادة: | 0 (Cytoskeletal Proteins) 0 (LAMP1 protein, human) 0 (Lysosomal Membrane Proteins) 0 (MIRN184 microRNA, human) 0 (MicroRNAs) 0 (ezrin) |
| تواريخ الأحداث: | Date Created: 20140925 Date Completed: 20150126 Latest Revision: 20231213 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1111/febs.13066 |
| PMID: | 25251993 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1742-4658 |
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| DOI: | 10.1111/febs.13066 |