MiR-221-3p regulates the microvascular dysfunction in diabetic retinopathy by targeting TIMP3
- PDF / 3,250,052 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 115 Downloads / 172 Views
MOLECULAR AND CELLULAR MECHANISMS OF DISEASE
MiR-221-3p regulates the microvascular dysfunction in diabetic retinopathy by targeting TIMP3 Chongxian Wang 1 & Yuling Lin 2 & Yanqin Fu 1 & Dongming Zhang 1 & Yaping Xin 1 Received: 9 July 2019 / Revised: 11 June 2020 / Accepted: 2 July 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Diabetic retinopathy is one of the major complications of diabetes and the main cause to lead to blindness for diabetic patients. However, the exact mechanisms involved in the progression of diabetic retinopathy are not completely known. Herein, we demonstrated a novel role of miR-221-3p in the microvascular dysfunction in diabetic retinopathy. MiR-221-3p expression was found to be substantially upregulated in the retina samples of diabetic rats. Besides, ganglion cell layer, inner nuclear layer, outer nuclear layer, and retinal pigment epithelium layer of diabetic rats expressed higher miR-221-3p than the matched areas of normal rats. High glucose-treated retinal microvascular endothelial cells RF/6A and HRECs exhibited higher miR-221-3p than that in normal condition. MiR-221-3p inhibition could alleviate the retinal vascular leakage induced by diabetes in vivo as evaluated by Evans blue leakage assay, and reduce the proliferation, accelerate the apoptosis development, and inhibit the migration capacity of high glucose-treated RF/6A cells in vitro, while miR-221-3p overexpression partially enhanced the detrimental effects. By bioinformatics analysis and luciferase reporter assay, we identified that TIMP3 is the direct target of miR-221-3p. TIMP3 overexpression counteracted the effect of miR-221-3p on the vessel leakage and endothelial cell function. In conclusion, this study highlights the negative role of miR-221-3p in the microvascular dysfunction in diabetic retinopathy by targeting TIMP3, representing a potential therapeutic target for human diabetic retinopathy. Keywords MiR-221-3p . Diabetic retinopathy . TIMP3 . Vessel leakage . Endothelial cells
Introduction Diabetic retinopathy (DR) is one of the major complications of diabetes and the main cause to lead to blindness for diabetic patients. The vessel leakage of retinal microvasculature and pathological angiogenesis are the main events in diabetic retinopathy [17, 29]. Hyperglycemia can induce progressive injury to the retinal microvasculature, resulting in the damaged permeability and leakage of the retinal microvasculature as well as microvasculature dysfunction. The chronic damage of DR also induces the compensatory neovascularization on the surface of Chongxian Wang and Yuling Lin contributed equally to this work. * Yuling Lin [email protected] 1
Department of Endocrinology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450002, China
2
Department of Endocrinology, Nanyang City Center Hospital, Nanyang 473000, China
the retina, which may ultimately cause the severe ocular angiogenesis and consequent loss of vision in diabetic patients [13]. As yet, there is no effective treatm
Data Loading...
