*9.4. miR-486-5p*

One of the most serious causes of acute kidney injury is ischemia-reperfusion injury, often resulting in tubular cell necrosis or apoptosis. In one experimental study (Viñas et al., 2016), the effect of exosomes with *miR-486-5p* derived from endothelial colony-forming cells (ECFCs) on protection against kidney injury was investigated in mice with induced renal ischemia. Infusion of ECFC exosomes into ischemic endothelial kidney cells had a strong functional and histological protective effect, associated with increased kidney *miR-486-5p* levels, decreased phosphatase and tensin homolog (*PTEN*) and activation of the *Akt* pathway [75]. In chronic kidney disease, *miR-486-5p* inhibits the forkhead transcription factor *FOXO1* by downregulation of *PTEN* phosphatase, a negative regulator of *Akt*. *FOXO1* appears to be the predominant mediator of muscle wasting in chronic nephropathy, accelerated by stimulating the ubiquitin proteasome system through activation, e.g., E3 ligases [76]. In one human study (Regmi et al., 2019) involving patients with diabetic nephropathy, decreased serum concentrations of *miR-486-5p* were found and, this negatively correlated with albuminuria, levels of fasting blood glucose and glycated hemoglobin [77].

The association between LPS-induced inflammation and *miR-486-5p* with target *FOXO1* has been studied in vitro in nucleus pulposus cells and intervertebral disc degeneration. Experimentally, it was shown that *miR-486-5p* overexpression led to a decrease of LPS-induced production of inflammatory cytokines IL-1ß, IL-6 and TNFα and protected the nucleus pulposus cells against apoptosis [78].
