Key result
Knockdown of NEAT1 reduced high-glucose-triggered oxidative stress, apoptosis, and inflammation in human retinal endothelial cells by inactivating TGF-β1 and VEGF signaling pathways.
Why the study?
Although lncRNA NEAT1 plays regulatory roles in various diseases, its implications in diabetic retinopathy remained barely known.
Knockdown of NEAT1 suppresses diabetic retinopathy progression in preclinical models by inactivating TGF-β1 and VEGF signaling pathways.
Hypothesis-generating for NEAT1 targeting in diabetic retinopathy; leaves open clinical translation and should not yet change practice.
Diabetic retinopathy (DR) is complication resulted from Type 2 diabetes mellitus. Accumulating evidence has proved the functions of long noncoding RNAs (lncRNAs) in the progression of DR. Recent reports exert the numerous regulatory functions of lncRNA nuclear-enriched abundant transcript 1 (NEAT1) in various diseases. However, its implications in DR remain barely known. Therefore, this study was carried out to explore the role of NEAT1 in high-glucose (HG)-triggered injury of human retinal endothelial cells (hRECs). Here, we found the NEAT1 level was significantly elevated in patients with DR, in the retina of diabetic rats and mice. Meanwhile, hRECs under HG stimuli also exhibited an increase of NEAT1. Moreover, the loss of NEAT1 enhanced hRECs proliferation and repressed HG-induced apoptosis, which was accompanied by an upregulation of Bcl-2 and a downregulation of Bax. Subsequently, the knockdown of NEAT1 obviously reduced HG-triggered oxidative stress injury in hRECs. It was reflected that intracellular reactive oxygen species and malondialdehyde level induced by HG were repressed by NEAT1 downregulation, while superoxide dismutase activity was increased. In addition, decreased NEAT1 repressed the inflammatory processes effectively as indicated by the inactivation of inflammatory cytokines Cox-2, interleukin-6, and tumor necrosis factor-α. Furthermore, vascular endothelial growth factor A (VEGF) and transforming growth factor-β1 (TGF-β1) expression in patients with DR, DR rats, and HG-incubated hRECs was obviously increased. The silence of NEAT1 could reduce the enhanced expression of VEGF and TGF-β1 induced by HG. Hence, we concluded NEAT1 might contribute to the development of DR through activating TGF-β1 and VEGF.
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Shao et al. (2020) studied Diabetic retinopathy. Knockdown of NEAT1 vs. High-glucose stimuli without NEAT1 knockdown was evaluated on High-glucose-triggered injury (apoptosis, oxidative stress, inflammation) in human retinal endothelial cells. Knockdown of NEAT1 reduced high-glucose-triggered oxidative stress, apoptosis, and inflammation in human retinal endothelial cells by inactivating TGF-β1 and VEGF signaling pathways.
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