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Related Concept Videos

MicroRNAs01:22

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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
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Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia. The four categories of diabetes are type 1 diabetes, type 2 diabetes, other specific types of diabetes, and gestational diabetes.
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MicroRNA-423 may regulate diabetic vasculopathy.

Arnon Blum1, Ari Meerson2,3, Hanan Rohana4

  • 1Vascular Research Laboratory, Department of Medicine, Azrieli Faculty of Medicine, Baruch Padeh Medical Center, Bar-Ilan University, 15208, Lower Galilee, Israel. ablum@poria.health.gov.il.

Clinical and Experimental Medicine
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Lowered microRNA-423 (miR-423) levels in patients with proliferative diabetic retinopathy correlate with vascular endothelial growth factor (VEGF) and nitric oxide (NO) pathways, suggesting a role in diabetic eye disease progression.

Keywords:
NONO-dependent pathwaysVEGFmiR-423

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Area of Science:

  • Ophthalmology
  • Endocrinology
  • Molecular Biology

Background:

  • Diabetic retinopathy (DR) is a leading cause of vision loss in type 2 diabetes mellitus (T2DM).
  • MicroRNAs (miRNAs) are implicated in various cellular processes, including vascular complications.
  • Understanding the molecular mechanisms of DR is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the role of specific miRNAs, vascular endothelial growth factor (VEGF), nitric oxide (NO), and total antioxidant capacity (TAO) in T2DM patients with varying stages of retinopathy.
  • To explore potential correlations between these markers and the development/progression of diabetic retinopathy.

Main Methods:

  • Serum levels of 16 candidate miRNAs, VEGF, NO, and TAO were measured in 69 participants (healthy, T2DM without retinopathy, nonproliferative DR, proliferative DR).
  • mRNA levels of key genes (e.g., eNOS, VEGF, CRP, TNFα) were analyzed in endothelial cells cultured with pooled sera.
  • Statistical analyses were performed to identify significant associations.

Main Results:

  • Plasma miR-423 levels were significantly decreased in patients with proliferative diabetic retinopathy (PDR) compared to controls.
  • Patients with retinopathy showed higher NO, lower VEGF, and decreased TAO levels.
  • Endothelial nitric oxide synthase (eNOS) mRNA levels varied with disease stage, and PON2, p22, and SOD2 mRNA levels were lower in PDR.
  • Lowered miR-423 correlated with VEGF and inversely with NO and eNOS expression.

Conclusions:

  • A potential cross-talk exists between miR-423 and VEGF signaling, impacting eNOS function in diabetic retinopathy.
  • miR-423 may play a regulatory role in diabetic vascular retinal proliferation.
  • These findings highlight miR-423 as a potential biomarker and therapeutic target in diabetic retinopathy.