Possible Role of Endothelial-Derived Cellular and Exosomal-miRNAs in Lipid-Mediated Diabetic Retinopathy: Microarray Studies.

Autor: Elmasry K; Department of Oral Biology and Diagnostic Sciences, The Dental College of Georgia, Augusta University, Augusta, GA 30912, USA.; DCG Center for Excellence in Research, Scholarship, and Innovation (CERSI), Augusta University, Augusta, GA 30912, USA.; Department of Cellular Biology and Anatomy, The Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.; Department of Human Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt., Habib S; Department of Oral Biology and Diagnostic Sciences, The Dental College of Georgia, Augusta University, Augusta, GA 30912, USA.; DCG Center for Excellence in Research, Scholarship, and Innovation (CERSI), Augusta University, Augusta, GA 30912, USA.; Department of Medical Parasitology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt., Helwa I; Department of Cellular Biology and Anatomy, The Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.; Department of Histopathology, Faculty of Oral and Dental Medicine, Misr International University, Cairo 19648, Egypt., Khaled ML; Department of Cellular Biology and Anatomy, The Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.; Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt., Ibrahim AS; Department of Ophthalmology, Visual, and Anatomical Sciences, School of Medicine, Wayne State University, Detroit, MI 48201, USA.; Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.; Department of Pharmacology, School of Medicine, Wayne State University, Detroit, MI 48201, USA., Tawfik A; Eye Research Institute, Oakland University, Rochester, MI 48309, USA.; Eye Research Center (OUWB)/ERC, William Beaumont School of Medicine, Rochester, MI 48073, USA.; Department of Foundational Medical Studies and Eye Research Center, Oakland University William Beaumont School of Medicine, Rochester, MI 48309, USA., Al-Shabrawey M; Eye Research Institute, Oakland University, Rochester, MI 48309, USA.; Eye Research Center (OUWB)/ERC, William Beaumont School of Medicine, Rochester, MI 48073, USA.; Department of Foundational Medical Studies and Eye Research Center, Oakland University William Beaumont School of Medicine, Rochester, MI 48309, USA.
Jazyk: angličtina
Zdroj: Cells [Cells] 2024 Nov 15; Vol. 13 (22). Date of Electronic Publication: 2024 Nov 15.
DOI: 10.3390/cells13221886
Abstrakt: 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.
Databáze: MEDLINE
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