The role of SIRT1 in diabetic retinopathy - 31/12/17
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Abstract |
The prevalence of diabetes mellitus (DM), has been increasing worldwide. Diabetic retinopathy (DR) is the most common microvascular complication in diabetes. It is a multifactorial disease that occurs primarily through the long-term detrimental effects of hyperglycemia. The pathogenesis of DR is complex, including inflammation, oxidative stress and advanced glycation end products (AGES).
SIRT1 is a nicotinamide adenosine dinucleotide (NAD+)-dependent deacetylase that removes acetyl groups from proteins which can be implicated in DR. Inhibition of miRNAs such as miR-23b- 3P and miR-34a and activation of adenosine monophosphate-activated protein kinas (AMPK) and Peroxisome proliferative-activated receptor α (PPARα), modulate inflammation by enhancing the level of SIRT1. SIRT1 activation leads to the down regulation of nuclear factor kappa-light-chain-enhancer of activated of B cells (NF-κB), and the downstream pathway including increased level of Interleukin-17 (IL-17) and other pro-inflammatory cytokines. Oxidative stress- induced apoptosis is due to activation of some transcriptional factors such as p53 and Protein arginine methyl transferase 1 (PRMIT1) which are inhibited by SIRT1. In addition to these, the increased level of some transcriptional factors such as, vascular endothelial growth factor (VEGF), hypoxia − induced factors (HIFs), transforming growth factor β1 (TGF-β1), endothelin-1 (ET-1), fork head box O 1 (FOXO1) and Notch signaling may be inhibited by activation of SIRT1 leads to attenuation of vascular dysfunction.
In conclusion, SIRT1 regulates apoptosis, inflammation and oxidative stress resulting in improving DR. This review focuses on the role of SIRT1 in DR.
Le texte complet de cet article est disponible en PDF.Abbreviations : SIR2, HDACs, NAD+, DM, AGEs, AMPK, TGFβ1, NF-κB, MMP-9, NO, RECS, TNF, ET-1, PPARα, ECM, FN, ICAM, NAMPT, GLP-1, RPE, NICD, HIFs, Th, PRMT1, PRMCs, mnSOD, GFAP, VEGF, FOXO
Keywords : Retinopathy, Diabetes, Oxidative stress, SIRT1
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Vol 97
P. 190-194 - janvier 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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