| Modulation of inflammatory markers by miR-146a during replicative senescence in trabecular meshwork cells. | |
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MedLine Citation:
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PMID: 20053980 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: To investigate the alterations in microRNA (miRNA) expression during replicative senescence (RS) in human trabecular meshwork (HTM) cells. METHODS: Two HTM cell lines were serially passaged until they reached RS. Changes in expression of 30 miRNAs were assessed by real-time quantitative (q)-PCR. The effects of miR-146a on gene expression were analyzed with gene arrays and the results confirmed by real-time q-PCR. Protein levels of IRAK1 and PAI-1 were analyzed by Western blot and those of IL6 and IL8 by ELISA. Senescence-associated markers were monitored by flow cytometry and cell proliferation by BrdU incorporation. RESULTS: RS of HTM cells was associated with significant changes in expression of 18 miRNAs, including the upregulation of miR-146a. miR-146a downregulated multiple genes associated with inflammation, including IRAK1, IL6, IL8, and PAI-1, inhibited senescence-associated beta-galactosidase (SA-beta-gal) activity and production of intracellular reactive species (iROS), and increased cell proliferation. Overexpression of either IRAK1 or PAI-1 inhibited the effects of miR-146a on cell proliferation and iROS production in senescent cells. CONCLUSIONS: RS in HTM cells was associated with changes in miRNA expression that could influence the senescent phenotype. Upregulation of the anti-inflammatory miR-146a may serve to restrain excessive production of inflammatory mediators in senescent cells and limit their deleterious effects on the surrounding tissue. Among the different proteins repressed by miR-146a, the inhibition of PAI-1 may act to minimize the effects of senescence on the generation of iROS and growth arrest and prevent alterations of the extracellular proteolytic activity of the TM. |
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Authors:
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Guorong Li; Coralia Luna; Jianming Qiu; David L Epstein; Pedro Gonzalez |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-01-06 |
Journal Detail:
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Title: Investigative ophthalmology & visual science Volume: 51 ISSN: 1552-5783 ISO Abbreviation: Invest. Ophthalmol. Vis. Sci. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-20 Completed Date: 2010-06-11 Revised Date: 2011-03-03 |
Medline Journal Info:
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Nlm Unique ID: 7703701 Medline TA: Invest Ophthalmol Vis Sci Country: United States |
Other Details:
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Languages: eng Pagination: 2976-85 Citation Subset: IM |
Affiliation:
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Department of Ophthalmology, Duke University, Durham, North Carolina 27710, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Blotting, Western Cell Aging / genetics* Cell Line Cell Proliferation Enzyme-Linked Immunosorbent Assay Flow Cytometry Gene Expression Profiling Genetic Markers Humans Interleukin-1 Receptor-Associated Kinases / metabolism Interleukin-6 / metabolism Interleukin-8 / metabolism Membrane Potential, Mitochondrial MicroRNAs / genetics* Middle Aged Oligonucleotide Array Sequence Analysis Plasminogen Activator Inhibitor 1 / metabolism Reactive Oxygen Species / metabolism Reverse Transcriptase Polymerase Chain Reaction Tissue Donors Trabecular Meshwork / cytology*, metabolism* Transfection |
| Grant Support | |
ID/Acronym/Agency:
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EY016228/EY/NEI NIH HHS; EY01894/EY/NEI NIH HHS; EY05722/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Genetic Markers; 0/Interleukin-6; 0/Interleukin-8; 0/MIRN146 microRNA, human; 0/MicroRNAs; 0/Plasminogen Activator Inhibitor 1; 0/Reactive Oxygen Species; 0/SERPINE1 protein, human; EC 2.7.1.37/IRAK1 protein, human; EC 2.7.11.1/Interleukin-1 Receptor-Associated Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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