Premium
Knockdown of NEAT1 exerts suppressive effects on diabetic retinopathy progression via inactivating TGF‐β1 and VEGF signaling pathways
Author(s) -
Shao Kan,
Xi Liuqing,
Cang Zhen,
Chen Cheng,
Huang Shan
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29740
Subject(s) - downregulation and upregulation , gene knockdown , malondialdehyde , transforming growth factor , superoxide dismutase , oxidative stress , diabetic retinopathy , apoptosis , cancer research , vascular endothelial growth factor , chemistry , tumor necrosis factor alpha , vascular endothelial growth factor a , proinflammatory cytokine , endocrinology , medicine , microbiology and biotechnology , diabetes mellitus , biology , inflammation , biochemistry , vegf receptors , gene
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.