Regulation of the Nrf2 antioxidant pathway by microRNAs: New players in micromanaging redox homeostasis

Enhanced Reactive Oxygen Species Production, Acidic Cytosolic pH and Upregulated Na+/H+ Exchanger (NHE) in Dicer Deficient CD4+ T Cells

“…microRNAs are able to buffer the regulation of these events by directly interacting with the Nrf2 pathway and the generation of reactive oxygen species (ROS) [25]. In endothelial cells, many biological functions such as generation of ROS and redox reactions are regulated by miRNAs and thus, sensitive to Dicer [25, 26].…”

NFE2L2 (nuclear factor, erythroid 2-like 2)

“…It is not known whether it has a role in the regulation of NFE2L2 expression. Micro RNAs species reported to suppress NFE2L2 expression include miR-27a, miR-28, miR-34a, miR-93, miR-142-5p, miR-144, and miR-153 (Filipowicz et al, 2008;Cheng et al, 2013;Hayes and DinkovaKostova, 2014).…”

Nrf2 as an Endothelial Mechanosensitive Transcription Factor

“…112 It has been reported in a variety of cell types that redox-sensitive micro-RNAs (redoxi-miRs) can modulate levels of Nrf2 and the regulators of Nrf2 signaling, ARE-associated antioxidant gene expression, and the enzymes involved in ROS generation. 6,56,113 Given that FSS patterns are major physiological and pathophysiological stimuli that induce or suppress an array of pro-and anti-inflammatory genes in EC, it is likely that mechanosensitive micro-RNAs are involved in the regulation of endothelial redox and inflammatory phenotype. 114,115 Micro-RNA expression profiles have been shown to be differentially regulated in EC exposed to laminar and oscillatory FSS patterns, [116][117][118] leading to alterations in both pro-and anti-inflammatory gene expression, and thus may constitute an additional factor that contributes to atherogenesis.…”

“…Additional studies are necessary for the identification of mechanosensitive redoxi-miRs and elucidation of the mechanisms by which they regulate Nrf2/ARE signaling and antioxidant gene expression in EC exposed to FSS to fully assess the potential of micro-RNAs as therapeutic targets to prevent or treat atherosclerosis. [112][113][114]119 The evidence linking Nrf2 signaling to FSS patterns is unequivocal and mediated by a change in EC redox status, resulting in enhanced antioxidant gene induction thereby maintaining redox homeostasis. The likely regulation of key mediators of the Nrf2 pathway by redoxi-miRs 113 and mechanosensitive micro-RNAs, as well as potentially long noncoding RNAs, 129 add an additional dimension to provide fine tuning of EC redox signaling (Figure 2).…”