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

• Published in: Redox report : communications in free radical research Vol. 27; no. 1; pp. 70 - 78
• Main Authors: Atef, Marwa Mohamed, Shafik, Noha M., Hafez, Yasser Mostafa, Watany, Mona Mohamed, Selim, Amal, Shafik, Heba M., Safwat El-Deeb, Omnia
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 31.12.2022; Taylor & Francis Group
• Subjects: angiogenesis; Diabetes Mellitus; Diabetic retinopathy; Diabetic Retinopathy - genetics; endoglin; HIF-1α; HIF1A-AS2; Humans; Hypoxia - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; MAPK; Mitogen-Activated Protein Kinases - metabolism; oxidative stress; Oxidative Stress - genetics; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; VEGF; Diabetic retinopathy; VEGF; angiogenesis; HIF1A-AS2; HIF-1α; endoglin; MAPK; oxidative stress
• ISSN: 1351-0002; 1743-2928; 1743-2928
• DOI: 10.1080/13510002.2022.2050086

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. 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. 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. 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.