Biao Yan1, Jin Yao1, Jingyu Liu1, Xiu‐Miao Li1, Xiaoqun Wang1, Yujie Li1, Zhi‐Fu Tao1, Yu‐Chen Song1, Qi Chen1, Qin Jiang1
1From the Department of Central Laboratory, Eye Hospital (B.Y., J.-Y.L., J.Y., X.-M.L., X.-Q.W., Y.-J.L., Z.-F.T., Y.-C.S., Q.J.), Department of Ophthalmology, The Fourth School of Clinical Medicine (B.Y., J.Y., Q.J.), and Department of Pathophysiology, School of Basic Medical Sciences (Q.C.), Nanjing Medical University, Nanjing, China.
Tóm tắt
Rationale:
Pathological angiogenesis is a critical component of diseases, such as ocular disorders, cancers, and atherosclerosis. It is usually caused by the abnormal activity of biological processes, such as cell proliferation, cell motility, immune, or inflammation response. Long noncoding RNAs (lncRNAs) have emerged as critical regulators of these biological processes. However, the role of lncRNA in diabetes mellitus–induced microvascular dysfunction is largely unknown.
Objective:
To elucidate whether lncRNA-myocardial infarction–associated transcript (MIAT) is involved in diabetes mellitus–induced microvascular dysfunction.
Methods and Results:
Using quantitative polymerase chain reaction, we demonstrated increased expression of lncRNA-MIAT in diabetic retinas and endothelial cells cultured in high glucose medium. Visual electrophysiology examination, TUNEL staining, retinal trypsin digestion, vascular permeability assay, and in vitro studies revealed that MIAT knockdown obviously ameliorated diabetes mellitus–induced retinal microvascular dysfunction in vivo, and inhibited endothelial cell proliferation, migration, and tube formation in vitro. Bioinformatics analysis, luciferase assay, RNA immunoprecipitation, and in vitro studies revealed that MIAT functioned as a competing endogenous RNA, and formed a feedback loop with vascular endothelial growth factor and miR-150-5p to regulate endothelial cell function.
Conclusions:
This study highlights the involvement of lncRNA-MIAT in pathological angiogenesis and facilitates the development of lncRNA-directed diagnostics and therapeutics against neovascular diseases.
