Objective  To explore whether or not an inhibition of USP14 can attenuate acute renal injury induced by ischemia reperfusion （I/R） and elucidate its underlying mechanisms.

Methods  An in vivo renal I/R model was established by clamping left-sided renal artery for 45 min and recanalization. Renal tissue injury was observed in each group after hematoxylin-eosin （HE） stain. Serum levels of blood urea nitrogen （BUN） and creatinine （Scr） were measured by biochemical kits. The expressions of endoplasmic reticulum （ER） stress-related proteins （GRP78, CHOP, IRE1 & JNK） and apoptosis-related proteins （cleaved caspase-3 & Bcl-2） were detected by Western blot. Apoptotic level of renal tissue cells was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling （TUNEL）.

Results  As compared with sham group, renal injury and renal dysfunction in I/R group became gradually worse in a time-dependent manner during reperfusion phase and the expression of USP14 and the levels of BUN and Scr spiked in kidney tissue （P＜0.05）; Compared with I/R+sh-NC group, renal pathological injury and the levels of USP14, BUN and Scr declined in kidney tissues in I/R+sh-USP14 group （P＜0.05）. In addition, compared with sham group, renal cell apoptosis, the expressions of cleaved caspase-3 and GRP78, CHOP, IRE1 & p-JNK rose and Bcl-2 declined in kidney tissues in I/R group （P＜0.05）; Compared with I/R+sh-NC group, renal cell apoptosis, down-regulations of cleaved caspase-3 and endoplasmic reticulum （ER） stress-related proteins and up-regulation of Bcl-2 were observed in kidney tissues in I/R+sh-USP14 group （P＜0.05）.

Conclusions  An inhibition of USP14 ameliorates ER stress, apoptosis and protein expression of IRE1/JNK pathway, thereby attenuating renal I/R injury.