*9.5. miR-423-5p*

Ischemia-reperfusion-induced AKI is one possible pathophysiological process, in which *miR-423-5p* may be substantially involved, along with other circulating miRNAs. Experimentally, it has been shown that *miR-423-5p* induces endoplasmic reticulum stress and reactive oxidative stress by inhibiting the *GSTM1* (Glutathione-S-Transferase Mu 1) gene which encodes the glutathione-S-transferase M1 enzyme in ischemia-reperfusion injury [79]. Glutathione-S-transferase is a very potent detoxification enzyme that protects the renal tubular cells against oxidative stress and ROS. The considerable involvement of *miR-423-5p* in the regulation and activation of NF-κB signaling by the *TNIP2* gene has been demonstrated in patients with lupus nephritis [80]. The *TNIP2* gene increases IKKα kinase activity and phosphorylation and induces NF-κB target genes [80]. The exact pathogenesis and factors contributing to renal cell injury here are still under investigation. *MiR-423-5p* is postulated to suppress podocyte injury in conditions of high blood glucose levels. Overexpression of *miR-423-5p*

by negatively regulated Nicotinamide adenine dinucleotide phosphate oxidase-4 (*NOX4*) gene can antagonize high glucose-induced podocyte injury. Moreover, it inhibits ROS production, cell apoptosis, inflammation and subsequent damage of renal cells [81].

The schematic pathophysiology of acute kidney injury in a critically ill patient with sepsis and nephrotoxic antibiotic treatment with selected miRNAs is presented in Figure 2.

**Figure 2.** Schematic pathophysiology of acute kidneyinjuryin a criticallyill patientwith sepsis and nephrotoxic antibiotic treatment with selected miRNAs. AKI—acute kidney injury, *GSTM1*—glutathione-S-transferase Mu 1 gene, IL-6—interleukin 6, IL-1ß—interleukin 1ß, NF-κB—nuclear factor—kappa B, TNFα—tumor necrosis factor alpha, *TNIP2*—tumor necrosis factor alpha induced protein 3-interacting protein 2, TLR4—Toll-like receptor 4.
