miR‐26a modulates HGF and STAT3 effects on the kidney repair process in a glycerol‐induced AKI model in rats

Acute kidney injury is mostly reversible, and hepatocyte growth factor (HGF) has a relevant role in the tissue repair. MicroRNA (miR)‐26a is an endogenous modulator of HGF. The role of miR‐26a in the kidney repair process was evaluated in Wistar rats submitted to an acute kidney injury model of rhabdomyolysis induced by glycerol (6 mL/kg). Animals were evaluated 3, 12, 48, 96, and 120 hours after glycerol injection. Serum creatinine (SCr) and gene expression of HGF, c‐met, signal transducer and activator of transcription 3 (STAT3), and miR‐26a were estimated. Also, tubular NK52E cells were transfected with anti‐miR26a and stimulated with Fe3+ for 24 hours to mimic the effects of myoglobin in vitro. SCr was highest after 48 hours. After 96 hours, SCr started to decrease, characterizing the recovery phase, with normalization after 120 hours. HGF expression increased during the onset phase (3 hours), with a low relationship with miR‐26a. In contrast, in the recovery phase, the increase in miR‐26a was coincident with HGF messenger RNA suppression, suggesting that in the recovery phase, miR‐26a may have a role in HGF modulation. Fe3+ induced cellular death after 3 hours and proliferation after 24 hours. There was no correlation between miR‐26a and STAT3 during the death phase; however, during the proliferation phase, an increase in STAT3 was paralleled with a decrease in miR‐26a. miR‐26a silencing induced increases in cell viability and the phosphorylated form of STAT3 protein expression in cells receiving Fe3+. In conclusion, miR‐26a may have a key role in modulating HGF levels after its proliferative effects have been triggered. In both in vivo and in vitro models, we found 2 distinct phases: an onset or damage phase and a recovery or proliferative phase. The results suggest that the upregulation of hepatocyte growth factor and signal transducer and activator of transcription 3 in acute kidney injury induced by rhabdomyolysis is not dependent on microRNA‐26a; microRNA‐26a may have a role as a negative feedback control of hepatocyte growth factor translation during the recovery/proliferative phase.