FP280FUNCTIONAL INVESTIGATION OF MIR-17-5P INHIBITION IN KIDNEY ISCHEMIA-REPERFUSION INJURY IN MICE

INTRODUCTION: : One of the most common causes of acute kidney injury (AKI) is ischemia-reperfusion (IR), which increases the risk of renal fibrosis and chronic kidney disease. Our group has previously described the activation of the pro-proliferative and anti-apoptotic miR-17-5p in IR induced AKI. Our aim was to investigate the function of miR-17-5p in IR-induced renal fibrosis in mice. METHODS: : AKI was induced in the left kidneys of C57BL / 6N mice with 20-minute ischemia, without the removal of the right intact kidney. One day before the IR operation, mice were given miR-17-5p silencing (17-LNA-IR group, N = 10) or scrambled sequence (SCR-IR group, N = 10) locked nucleic acid (LNA) modified antisense oligonucleotides (30 mg / kg, ip). On the 7th reperfusion day, the efficacy of the miR-17-5p inhibition was evaluated in the injured and control kidneys (qPCR). We investigated the extent of tubular damage in histological sections (PAS, HE) and KIM1 mRNA, the miR-17-5p-target p21 mRNA expression, fibrosis (FN1 mRNA), inflammation (TNFα mRNA), the oxidative stress response (NRF2 mRNA), and the cell-proliferation (PCNA mRNA) with real-time PCR. RESULTS: At the 7th reperfusion day, specific LNA inhibition prevented the increase in miR-17-5p expression (1.62x, p <0.01, SCR-IR vs. non-IR) in the damaged kidneys (0.49x, p < 0.0001; 17-LNA-IR vs. SCR-IR). The inhibition of miR-17-5p following IR had no significant effect either on the histological damage, or on increased KIM1 (83.2x, p <0.0001), FN1 (8.6x, p <0.0001), TNFα (5.8x, p < 0.0001), NRF2 (1.4x, p <0.01), PCNA (1.3x, p <0.05), and p21 (3.8x, p <0.0001) mRNA levels. CONCLUSIONS: While miR-17-5p could have renoprotective effects, our findings suggest that miR-17-5p inhibition has no significant effects on the IR-induced AKI outcome. Supported by the ÚNKP-17-4-I-SE-79 New National Excellence Program of the Ministry of Human Capacities