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. 2022 Dec;27(1):70-78.
doi: 10.1080/13510002.2022.2050086.

The evolving role of long noncoding RNA HIF1A-AS2 in diabetic retinopathy: a cross-link axis between hypoxia, oxidative stress and angiogenesis via MAPK/VEGF-dependent pathway

Marwa Mohamed Atef  1 , Noha M Shafik  1 , Yasser Mostafa Hafez  2 , Mona Mohamed Watany  3 , Amal Selim  2 , Heba M Shafik  4 , Omnia Safwat El-Deeb  1
Affiliations

The evolving role of long noncoding RNA HIF1A-AS2 in diabetic retinopathy: a cross-link axis between hypoxia, oxidative stress and angiogenesis via MAPK/VEGF-dependent pathway

Marwa Mohamed Atef et al. Redox Rep. 2022 Dec.

Abstract

Background: Diabetic retinopathy (DR) signifies a frequent serious diabetic complication influencing retinal structure and function. Dysregulation of lncRNAs drives a wide array of human diseases especially diabetes; thus, we aimed to study lncRNA HIF1A-AS2 role and its interplay with hypoxia, oxidative stress (OS), and angiogenesis in DR.

Materials and methods: 60 DM patients in addition to 15 healthy subjects. were enrolled. LncRNA HIF1A-AS2 mRNA relative gene expression was assessed. Hypoxia inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), mitogen activated protein kinase (MAPK), and endoglin levels were assessed. Detection of DNA damage using comet assay, and Redox status parameters were also detected.

Results: LncRNA HIF1A-AS2 expression was significantly increased in diabetic patients with the highest levels in proliferative DR patients. Moreover, HIFα, VEGF, MAPK, and Endogolin levels were significantly higher in the diabetic patients compared to control group with the highest levels in in proliferative DR patients. Significant DNA damage in comet assay was observed to be the highest in this group.

Conclusion: We observed for the first time the imminent role of long noncoding RNA HIF1A-AS2 in DR throughout its stages and its interplay with hypoxia, OS, and angiogenesis via MAPK/VEGF-dependent pathway.

Keywords: Diabetic retinopathy; HIF-1α; HIF1A-AS2; MAPK; VEGF; angiogenesis; endoglin; oxidative stress.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Photomicrographs representation of DNA damage in peripheral blood mononuclear cells using comet assay in control group (A), diabetic group without retinopathy (B), nonproliferative diabetic retinopathy group (C), proliferative diabetic retinopathy group (D). (The scale bar is 40 µm, 5 fields were assessed to provide this representative image).
Figure 2.
Figure 2.
HIF1A–AS2 relative expression in the studied groups. Data are represented as mean ± SD. * Significant difference vs. control group (P < 0.05). # Significant difference vs. diabetic group without retinopathy (P < 0.05). ▴Significant difference vs. nonproliferative diabetic retinopathy group (P < 0.05). ◊ Significant difference vs. proliferative diabetic retinopathy group (P < 0.05).
See this image and copyright information in PMC

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