Abstract

Diabetic retinopathy (DR) is a complication of diabetes mellitus (DM) and is the leading cause of vision loss globally. However, the pathogenic mechanism and clinical therapy still needs further improvement. The biologic significance of myocardial infarction associated transcript (MIAT) in DR remains unknown. Here, we aim to explore the mechanism between MIAT and DR, which is essential for RD. Streptozotocin (STZ) was used to induce DM mice and high glucose was used to stimulate cells. ChIP was used to detect the binding activity between nuclear factor κB (NF-κB) and the promoter of the MIAT gene, luciferase activity assay was used to detect the target-specific selectivity between miR-29b and MIAT. The expressions of MIAT and p-p65 were increased in STZ-induced DM mice and high glucose stimulated rat retinal Müller cells (rMC-1) cells. ChIP results revealed that high glucose promoted the binding activity between NF-κB and MIAT, while Bay11-7082 acted as an inhibitor for NF-κB that suppressed the binding activity. miR-29b controled MIAT to regulate its expression and MIAT overexpression suppressed miR-29b, but promoted Sp1. High glucose stimulation increased the cell apoptosis and decreased the cell activity, while MIAT suppression reversed the effect induced by high glucose, however, miR-29b knockdown reversed the effects induced by MIAT suppression. Our results provided evidence that the mechanism of cell apoptosis in DR might be associated with the regulation of MIAT, however, miR-29b acted as a biomarker that was regulated by MIAT and further regulated cell apoptosis in DR.

Highlights

  • Diabetes mellitus (DM) is a complex metabolic disorder and remains a disease with high number of incidences worldwide, especially in the developed countries [1]

  • We examined the expression of myocardial infarction associated transcript (MIAT) and p-p65 by stimulation of retinal Muller cells (rMC)-1 cells with normal glucose or high glucose

  • To detect the binding activity of MIAT with its regulatory factor, we introduced a nuclear factor κB (NF-κB)-specific monoclonal antibody to chromatin immunoprecipitate DNA cross-linked to NF-κB-tagged proteins, and measured the enrichment of specific DNA sequences using real-time PCR after cells were stimulated by high glucose

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Summary

Introduction

Diabetes mellitus (DM) is a complex metabolic disorder and remains a disease with high number of incidences worldwide, especially in the developed countries [1]. About half of the DM patients are suffering from several complications, which bring great pain for the patients and the family. Diabetic retinopathy (DR) is one of the most important complications in DM, which is afflicting approximately 20% of adult diabetic patients and is a leading cause of vision loss globally [4]. An improvement has been made in the DR therapy in the recent years, the prognosis remains poor [5]. Exploring the potential mechanism underlying DM is essential for the clinical therapy

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