Possible Role of Endothelial-Derived Cellular and Exosomal-miRNAs in Lipid-Mediated Diabetic Retinopathy: Microarray Studies
Diabetic retinopathy (DR) is a salient cause of blindness worldwide. There is still an immense need to understand the pathophysiology of DR to discover better diagnostic and therapeutic modalities. Human retinal endothelial cells (HRECs) were treated with 15-HETE or D-glucose, then miRNAs were isola...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-11-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/13/22/1886 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850216709374345216 |
|---|---|
| author | Khaled Elmasry Samar Habib Inas Helwa Mariam Lotfy Khaled Ahmed S. Ibrahim Amany Tawfik Mohamed Al-Shabrawey |
| author_facet | Khaled Elmasry Samar Habib Inas Helwa Mariam Lotfy Khaled Ahmed S. Ibrahim Amany Tawfik Mohamed Al-Shabrawey |
| author_sort | Khaled Elmasry |
| collection | DOAJ |
| description | Diabetic retinopathy (DR) is a salient cause of blindness worldwide. There is still an immense need to understand the pathophysiology of DR to discover better diagnostic and therapeutic modalities. Human retinal endothelial cells (HRECs) were treated with 15-HETE or D-glucose, then miRNAs were isolated, and a microarray was performed. MirWALK 2 and Ingenuity Pathway Analysis (IPA) were used to analyze the microarray results. Exosomal miRNAs from 15-HETE-treated HRECs were isolated, microarrayed, and then imported into IPA for further analysis. The microarray results showed that 15-HETE downregulated 343 miRNAs and upregulated 297 miRNAs in HRECs. High glucose treatment induced a differential expression of HREC-miRNAs where 185 miRNAs were downregulated and 244 were upregulated. Comparing the impact of 15-HETE versus DG or diabetic mouse retina elaborated commonly changing miRNAs. Pathway and target analysis for miRNAs changed in 15-HETE-treated HRECs revealed multiple targets and pathways that may be involved in 15-HETE-induced retinal endothelial dysfunction. The HREC-exosomal miRNAs were differentially expressed after 15-HETE treatment, with 34 miRNAs downregulated and 45 miRNAs upregulated, impacting different cellular pathways. Here, we show that 15-HETE induces various changes in the cellular and exosomal miRNA profile of HRECs, highlighting the importance of targeting the 12/15 lipoxygenase pathway in DR. |
| format | Article |
| id | doaj-art-46719d08c07a486aaa0d5ed4b33c59b8 |
| institution | OA Journals |
| issn | 2073-4409 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-46719d08c07a486aaa0d5ed4b33c59b82025-08-20T02:08:14ZengMDPI AGCells2073-44092024-11-011322188610.3390/cells13221886Possible Role of Endothelial-Derived Cellular and Exosomal-miRNAs in Lipid-Mediated Diabetic Retinopathy: Microarray StudiesKhaled Elmasry0Samar Habib1Inas Helwa2Mariam Lotfy Khaled3Ahmed S. Ibrahim4Amany Tawfik5Mohamed Al-Shabrawey6Department of Oral Biology and Diagnostic Sciences, The Dental College of Georgia, Augusta University, Augusta, GA 30912, USADepartment of Oral Biology and Diagnostic Sciences, The Dental College of Georgia, Augusta University, Augusta, GA 30912, USADepartment of Cellular Biology and Anatomy, The Medical College of Georgia, Augusta University, Augusta, GA 30912, USADepartment of Cellular Biology and Anatomy, The Medical College of Georgia, Augusta University, Augusta, GA 30912, USADepartment of Ophthalmology, Visual, and Anatomical Sciences, School of Medicine, Wayne State University, Detroit, MI 48201, USAEye Research Institute, Oakland University, Rochester, MI 48309, USAEye Research Institute, Oakland University, Rochester, MI 48309, USADiabetic retinopathy (DR) is a salient cause of blindness worldwide. There is still an immense need to understand the pathophysiology of DR to discover better diagnostic and therapeutic modalities. Human retinal endothelial cells (HRECs) were treated with 15-HETE or D-glucose, then miRNAs were isolated, and a microarray was performed. MirWALK 2 and Ingenuity Pathway Analysis (IPA) were used to analyze the microarray results. Exosomal miRNAs from 15-HETE-treated HRECs were isolated, microarrayed, and then imported into IPA for further analysis. The microarray results showed that 15-HETE downregulated 343 miRNAs and upregulated 297 miRNAs in HRECs. High glucose treatment induced a differential expression of HREC-miRNAs where 185 miRNAs were downregulated and 244 were upregulated. Comparing the impact of 15-HETE versus DG or diabetic mouse retina elaborated commonly changing miRNAs. Pathway and target analysis for miRNAs changed in 15-HETE-treated HRECs revealed multiple targets and pathways that may be involved in 15-HETE-induced retinal endothelial dysfunction. The HREC-exosomal miRNAs were differentially expressed after 15-HETE treatment, with 34 miRNAs downregulated and 45 miRNAs upregulated, impacting different cellular pathways. Here, we show that 15-HETE induces various changes in the cellular and exosomal miRNA profile of HRECs, highlighting the importance of targeting the 12/15 lipoxygenase pathway in DR.https://www.mdpi.com/2073-4409/13/22/1886diabetic retinopathymiRNAsexosomesextracellular vesiclesretinal endothelial cellslipoxygenase |
| spellingShingle | Khaled Elmasry Samar Habib Inas Helwa Mariam Lotfy Khaled Ahmed S. Ibrahim Amany Tawfik Mohamed Al-Shabrawey Possible Role of Endothelial-Derived Cellular and Exosomal-miRNAs in Lipid-Mediated Diabetic Retinopathy: Microarray Studies Cells diabetic retinopathy miRNAs exosomes extracellular vesicles retinal endothelial cells lipoxygenase |
| title | Possible Role of Endothelial-Derived Cellular and Exosomal-miRNAs in Lipid-Mediated Diabetic Retinopathy: Microarray Studies |
| title_full | Possible Role of Endothelial-Derived Cellular and Exosomal-miRNAs in Lipid-Mediated Diabetic Retinopathy: Microarray Studies |
| title_fullStr | Possible Role of Endothelial-Derived Cellular and Exosomal-miRNAs in Lipid-Mediated Diabetic Retinopathy: Microarray Studies |
| title_full_unstemmed | Possible Role of Endothelial-Derived Cellular and Exosomal-miRNAs in Lipid-Mediated Diabetic Retinopathy: Microarray Studies |
| title_short | Possible Role of Endothelial-Derived Cellular and Exosomal-miRNAs in Lipid-Mediated Diabetic Retinopathy: Microarray Studies |
| title_sort | possible role of endothelial derived cellular and exosomal mirnas in lipid mediated diabetic retinopathy microarray studies |
| topic | diabetic retinopathy miRNAs exosomes extracellular vesicles retinal endothelial cells lipoxygenase |
| url | https://www.mdpi.com/2073-4409/13/22/1886 |
| work_keys_str_mv | AT khaledelmasry possibleroleofendothelialderivedcellularandexosomalmirnasinlipidmediateddiabeticretinopathymicroarraystudies AT samarhabib possibleroleofendothelialderivedcellularandexosomalmirnasinlipidmediateddiabeticretinopathymicroarraystudies AT inashelwa possibleroleofendothelialderivedcellularandexosomalmirnasinlipidmediateddiabeticretinopathymicroarraystudies AT mariamlotfykhaled possibleroleofendothelialderivedcellularandexosomalmirnasinlipidmediateddiabeticretinopathymicroarraystudies AT ahmedsibrahim possibleroleofendothelialderivedcellularandexosomalmirnasinlipidmediateddiabeticretinopathymicroarraystudies AT amanytawfik possibleroleofendothelialderivedcellularandexosomalmirnasinlipidmediateddiabeticretinopathymicroarraystudies AT mohamedalshabrawey possibleroleofendothelialderivedcellularandexosomalmirnasinlipidmediateddiabeticretinopathymicroarraystudies |