Protective Role of microRNA-200a in Diabetic Retinopathy Through Downregulation of PDLIM1

Abstract

Background Diabetic retinopathy (DR) is a most common microvascular complication and regarded as the leading cause of blindness in the working age population. The involvement of miR-200a in various disorders has become recognized, and the objective of this study was to identify the protective effect of miR-200a in the development of DR. Methods The contents of miR-200a and its potential target gene, PDZ and LIM domain protein 1 (PDLIM1), were detected in both in-vivo and in-vitro DR models. Retinal leakage and inflammatory factor concentrations were detected after vitreous injections of miR-200a/PDLIM1 vectors in mice. The cellular viability, apoptosis and cellular migration were investigated using trypan blue staining, flow cytometry and transwell assay with human retinal microvascular endothelial cells (HRMECs). Besides, the prediction and confirmation of miR-200a targeting PDLIM1 were conducted with bioinformation analyses and dual-luciferase reporter assay. Results Lower miR-200a and higher PDLIM1 levels were detected in both in-vivo and in-vitro DR models. Besides, it was found that miR-200a treatment would significantly inhibit retinal permeability and inflammatory factors. Through targeting PDLIM1, it was found that miR-200a could improve cellular viability, remit apoptotic status and reduce cellular migration significantly in high glucose-treated HRMECs. Conclusion Our results demonstrated that miR-200a could be used as a potential therapy target through down-regulating PDLIM1 in DR.

Dapagliflozin Reduces Apoptosis of Diabetic Retina and Human Retinal Microvascular Endothelial Cells Through ERK1/2/cPLA2/AA/ROS Pathway Independent of Hypoglycemic

“…In a high glucose environment, a series of negative results occur including pericytes loss, apoptosis and proliferation of endothelial cells (ECs), disruption of blood-retinal barrier (BRB), and retinal neovascularization in retinal tissue ( Wan et al, 2021 ), among which ECs play an indispensable role in maintaining the BRB and are the first cells to sense blood glucose changes ( Kim et al, 2019 ; Yang et al, 2020 ). Activated by high glucose, many of the pathways mentioned above lead to metabolic disorders and the burden of oxidative stress in ECs ( Elmasry et al, 2019 ), which are considered to be the main pathogenesis of DR (RA.…”

HDAC3 Inhibition Alleviates High-Glucose-Induced Retinal Ganglion Cell Death through Inhibiting Inflammasome Activation

“…As the leading cause of blindness in working aging, DR progression would lead to macular edema and retinal neovascularization and thus cause vision loss. Photocoagulation, vitrectomy, and antivascular endothelial growth factor (VEGF) drugs are now used in the management of DR; however, poor prognosis is detected in the cases with late-stage DR [3,4]. Considering the severe health damage of DR, there is an urgent need to detect the early event of DR and thus promote early intervention development.…”

miRNA, lncRNA and circRNA: Targeted Molecules Full of Therapeutic Prospects in the Development of Diabetic Retinopathy

“…In addition to VEGF, many miRNAs protect RMECs in the DR state through other signaling pathways. PDLIM1 is a cytoskeletal protein associated with stress fibers, and miR-200a can downregulate the expression of PDLIM1 in RMECs and reduce the apoptotic state of RMECs, decreasing retinal microvascular leakage ( 41 ), which implies that miR-200a may be an efficient therapeutic target for the early stage of DR. miR-148a-3p specifically binds to the 3’ untranslated regions of TGFB2 and FGF2, downregulates their expression, and reduces the apoptosis of microvascular epithelial cells in the HG state ( 42 ). OPN regulates the inflammatory response at multiple levels ( 43 ).…”