Expression and significance of microRNA-21 in acute kidney injury renal of mice

Abstract

Objective To investigate the expression and significance of microRNA-21(miR-21) in acute kidney injury mice model at the different time points following ischemic/reperfusion. Methods C57BL/6J mice were divided into 3 major groups: the control group (C group), sham operation group(S group) and ischemia-reperfusion group (IR group). Later 2 groups were divided into 9 sub-groups respectively according to the time following reperfusion.Automatic biochemical analyzer detected serum creatinine (Scr), blood urea nitrogen (BUN) level.HE staining detected renal pathological damage.Renal tubulointerstitial pathological score accessed pathological damage.Real time-PCR tested the expression of miR-21 and mitogen-activated protein kinase kinase 3(MKK3) mRNA in renal respectively.Immunohistochemistry staining tested expression of MKK3. Results IR group's Scr, BUN levels gradually increased following reperfusion, 24 h reached its peak, then gradually declined.The Scr, BUN level had statistically significant difference between IR group and S group at the same time subgroup from 3 h to 168 h following reperfusion(all P<0.01). The change of kidney damage and pathological changes of interstitial and tubular injury score consensus with renal function.miR-21 increased gradually in renal ischemia after reperfusion, 24 h peaked and then stabilized at this high level.miR-21 was positively correlated with pathological tubulointerstitial injury from 0 h to 168 h after reperfusion (r=0.969, P<0.05). IR group's MKK3 mRNA and protein expression rose sharply following ischemia/reperfusion, 24 h peaked, and then gradually decreased.From 3 h to 168 h, the expression of MKK3 mRNA and proteins had significant difference at each same time points subgroups between IR group and S group(all P<0.01). Conclusions miR-21 increases gradually in renal ischemia after reperfusion, 24 h peaked and then stabilized at this high level.miR-21 is positively correlated with pathological tubulointerstitial injury, which may be associated with the negative regulated relationship between miR-21 and MKK3. Key words: microRNA-21; Ischemia-reperfusion injury; Acute kidney injury; Mitogen-activated protein kinase kinase 3