MicroRNA-184 attenuates hypoxia and oxidative stress-related injury via suppressing apoptosis, DNA damage and angiogenesis in an in vitro age-related macular degeneration model

dc.authoridKurtdere, Kardelen/0000-0002-4611-3436
dc.authoridDoganlar, Zeynep Banu/0000-0002-1365-9897
dc.authorwosidKurtdere, Kardelen/KEE-9234-2024
dc.authorwosidDoganlar, Zeynep Banu/B-4845-2008
dc.contributor.authorAykutlu, Merve Sambel
dc.contributor.authorGuclu, Hande
dc.contributor.authorDoganlar, Zeynep Banu
dc.contributor.authorKurtdere, Ayse Kardelen
dc.contributor.authorDoganlar, Oguzhan
dc.date.accessioned2024-06-12T10:50:56Z
dc.date.available2024-06-12T10:50:56Z
dc.date.issued2022
dc.departmentTrakya Üniversitesien_US
dc.description.abstractAge-related macular degeneration (AMD) is one of the leading causes of blindness worldwide, particularly in developed countries. Recently, microRNAs (miRs) have become popular research area to develop new treatment options of AMD. However, interaction between hsa-miR-184 and AMD remain largely unexplored. In this study, sub-lethal levels of Deforoxamine Mesylate salt (DFX) and H2O2 were applied to ARPE-19 cells to establish a severe in vitro AMD model, via durable hypoxia and oxidative stress. We found that up-regulation of miR-184 level in AMD can suppress hypoxia-related angiogenic signals through HIF-1 alpha/VEGF/MMPs axis. Also, miR-184 suppressed the hypoxia sensor miR-155 and genes in the EGFR/PI3K/AKT pathway, which is an alternative pathway in angiogenesis. To investigate the mechanism behind this protective effect, we evaluated the impact of miR-184 on retinal apoptosis in a model of AMD. miR-184 inhibited retinal apoptosis by upregulating BCL-2 and downregulating pro-apoptototic BAX, TRAIL, Caspase 3 and 8 signals as well as p53. Taken together, miR-184 attenuates retinal cell damage induced by severe AMD pathologies through suppressing hypoxia, angiogenesis and apoptosis. The safety profile of miR-184 was observed to be similar to Bevacizumab, which is in wide use clinically, but miR-184 was found to provide a more effective therapeutic potential by regulating simultaneously multiple pathologies.en_US
dc.description.sponsorshipTrakya University Scientific Research Fund [TUBAP 2019/181]en_US
dc.description.sponsorshipThe Trakya University Scientific Research Fund provided support for this study (TUBAP 2019/181).en_US
dc.identifier.doi10.1016/j.tiv.2022.105413
dc.identifier.issn0887-2333
dc.identifier.issn1879-3177
dc.identifier.pmid35690295en_US
dc.identifier.scopus2-s2.0-85132421878en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org/10.1016/j.tiv.2022.105413
dc.identifier.urihttps://hdl.handle.net/20.500.14551/18182
dc.identifier.volume83en_US
dc.identifier.wosWOS:000833399900001en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherPergamon-Elsevier Science Ltden_US
dc.relation.ispartofToxicology In Vitroen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectAge Related Macular Degenerationen_US
dc.subjectARPE 19en_US
dc.subjectBevacizumaben_US
dc.subjectMir-155en_US
dc.subjectMir-184en_US
dc.subjectRetinal-Pigment Epitheliumen_US
dc.subjectEndothelial Growth-Factoren_US
dc.subjectDown-Regulationen_US
dc.subjectRpe Cellsen_US
dc.subjectExpressionen_US
dc.subjectBevacizumaben_US
dc.subjectProgressionen_US
dc.subjectTherapyen_US
dc.subjectAtrophyen_US
dc.subjectCanceren_US
dc.titleMicroRNA-184 attenuates hypoxia and oxidative stress-related injury via suppressing apoptosis, DNA damage and angiogenesis in an in vitro age-related macular degeneration modelen_US
dc.typeArticleen_US

Dosyalar