microRNA-96 targets the INS/AKT/GLUT4 signaling axis: Association with and effect on diabetic retinopathy
Background: miR-96-5p is a highly expressed microRNA in the retina of subjects with diabetes. The INS/AKT/GLUT4 signaling axis is the main cell signaling pathway of glucose uptake in cells. Here, we investigated the role of miR-96-5p in this signaling pathway. Methods: Expression levels of miR-96-5p...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023027469 |
| _version_ | 1797815712034586624 |
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| author | Narges Zolfaghari Zahra-Soheila Soheili Shahram Samiei Hamid Latifi-Navid Ali Hafezi-Moghadam Hamid Ahmadieh Mozhgan Rezaei-Kanavi |
| author_facet | Narges Zolfaghari Zahra-Soheila Soheili Shahram Samiei Hamid Latifi-Navid Ali Hafezi-Moghadam Hamid Ahmadieh Mozhgan Rezaei-Kanavi |
| author_sort | Narges Zolfaghari |
| collection | DOAJ |
| description | Background: miR-96-5p is a highly expressed microRNA in the retina of subjects with diabetes. The INS/AKT/GLUT4 signaling axis is the main cell signaling pathway of glucose uptake in cells. Here, we investigated the role of miR-96-5p in this signaling pathway. Methods: Expression levels of miR-96-5p and its target genes were measured under high glucose conditions, in the retina of streptozotocin-induced diabetic mice, in the retina of AAV-2-eGFP-miR-96 or GFP intravitreal injected mice and in the retina of human donors with diabetic retinopathy (DR). MTT, wound healing, tube formation, Western blot, TUNEL, angiogenesis assays and hematoxylin-eosin staining of the retinal sections were performed. Results: miR-96-5p expression was increased under high glucose conditions in mouse retinal pigment epithelial (mRPE) cells, in the retina of mice receiving AAV-2 carrying miR-96 and STZ-treated mice. Expression of the miR-96-5p target genes related to the INS/AKT/GLUT4 signaling pathway was reduced following miR-96-5p overexpression. mmu-miR-96-5p expression decreased cell proliferation and thicknesses of retinal layers. Cell migration, tube formation, vascular length, angiogenesis, and TUNEL-positive cells were increased. Conclusions: In in vitro and in vivo studies and in human retinal tissues, miR-96-5p regulated the expression of the PIK3R1, PRKCE, AKT1, AKT2, and AKT3 genes in the INS/AKT axis and some genes involved in GLUT4 trafficking, such as Pak1, Snap23, RAB2a, and Ehd1. Because disruption of the INS/AKT/GLUT4 signaling axis causes advanced glycation end product accumulation and inflammatory responses, the inhibition of miR-96-5p expression could ameliorate DR. |
| first_indexed | 2024-03-13T08:26:49Z |
| format | Article |
| id | doaj.art-75a1509a4ce5455fb50b0d454d980a45 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-13T08:26:49Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-75a1509a4ce5455fb50b0d454d980a452023-05-31T04:44:42ZengElsevierHeliyon2405-84402023-05-0195e15539microRNA-96 targets the INS/AKT/GLUT4 signaling axis: Association with and effect on diabetic retinopathyNarges Zolfaghari0Zahra-Soheila Soheili1Shahram Samiei2Hamid Latifi-Navid3Ali Hafezi-Moghadam4Hamid Ahmadieh5Mozhgan Rezaei-Kanavi6Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology, Tehran, IranDepartment of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran; Corresponding author. Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology (NIGEB), Shahrak-e- Pajoohesh, 15th Km, Tehran -Karaj Highway, Tehran. P.O. Box: 14965/161, Iran.Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, IranDepartment of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology, Tehran, IranMolecular Biomarkers Nano-Imaging Laboratory, Brigham and Women's Hospital, Boston, MA, USAOphthalmic Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, IranOcular Tissue Engineering Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, IranBackground: miR-96-5p is a highly expressed microRNA in the retina of subjects with diabetes. The INS/AKT/GLUT4 signaling axis is the main cell signaling pathway of glucose uptake in cells. Here, we investigated the role of miR-96-5p in this signaling pathway. Methods: Expression levels of miR-96-5p and its target genes were measured under high glucose conditions, in the retina of streptozotocin-induced diabetic mice, in the retina of AAV-2-eGFP-miR-96 or GFP intravitreal injected mice and in the retina of human donors with diabetic retinopathy (DR). MTT, wound healing, tube formation, Western blot, TUNEL, angiogenesis assays and hematoxylin-eosin staining of the retinal sections were performed. Results: miR-96-5p expression was increased under high glucose conditions in mouse retinal pigment epithelial (mRPE) cells, in the retina of mice receiving AAV-2 carrying miR-96 and STZ-treated mice. Expression of the miR-96-5p target genes related to the INS/AKT/GLUT4 signaling pathway was reduced following miR-96-5p overexpression. mmu-miR-96-5p expression decreased cell proliferation and thicknesses of retinal layers. Cell migration, tube formation, vascular length, angiogenesis, and TUNEL-positive cells were increased. Conclusions: In in vitro and in vivo studies and in human retinal tissues, miR-96-5p regulated the expression of the PIK3R1, PRKCE, AKT1, AKT2, and AKT3 genes in the INS/AKT axis and some genes involved in GLUT4 trafficking, such as Pak1, Snap23, RAB2a, and Ehd1. Because disruption of the INS/AKT/GLUT4 signaling axis causes advanced glycation end product accumulation and inflammatory responses, the inhibition of miR-96-5p expression could ameliorate DR.http://www.sciencedirect.com/science/article/pii/S2405844023027469Diabetic retinopathyMmu-miR-96-5pRT-qPCRINS/AKT/GLUT4 signaling pathwayRecombinant AAV-2STZ induced Diabetic mice |
| spellingShingle | Narges Zolfaghari Zahra-Soheila Soheili Shahram Samiei Hamid Latifi-Navid Ali Hafezi-Moghadam Hamid Ahmadieh Mozhgan Rezaei-Kanavi microRNA-96 targets the INS/AKT/GLUT4 signaling axis: Association with and effect on diabetic retinopathy Heliyon Diabetic retinopathy Mmu-miR-96-5p RT-qPCR INS/AKT/GLUT4 signaling pathway Recombinant AAV-2 STZ induced Diabetic mice |
| title | microRNA-96 targets the INS/AKT/GLUT4 signaling axis: Association with and effect on diabetic retinopathy |
| title_full | microRNA-96 targets the INS/AKT/GLUT4 signaling axis: Association with and effect on diabetic retinopathy |
| title_fullStr | microRNA-96 targets the INS/AKT/GLUT4 signaling axis: Association with and effect on diabetic retinopathy |
| title_full_unstemmed | microRNA-96 targets the INS/AKT/GLUT4 signaling axis: Association with and effect on diabetic retinopathy |
| title_short | microRNA-96 targets the INS/AKT/GLUT4 signaling axis: Association with and effect on diabetic retinopathy |
| title_sort | microrna 96 targets the ins akt glut4 signaling axis association with and effect on diabetic retinopathy |
| topic | Diabetic retinopathy Mmu-miR-96-5p RT-qPCR INS/AKT/GLUT4 signaling pathway Recombinant AAV-2 STZ induced Diabetic mice |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023027469 |
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