CBX7 suppression prevents ischemia-reperfusion injury-induced endoplasmic reticulum stress through the Nrf-2/HO-1 pathway

Abstract

Renal ischemia/reperfusion injury (I/R) usually occurs in renal transplantation and partial nephrectomy, which could lead to acute kidney injury. However, the effective treatment for renal I/R still remains limited. In the present study, we investigated whether inhibition of CBX7 could attenuate renal I/R injury in vivo and in vitro, as well as the potential mechanisms. Adult male mice were subjected to right renal ischemia and reperfusion for different period, both with and without CBX7 inhibitor UNC3866. In addition, the human kidney cells (HK-2) were placed in hypoxia-reoxygenation (H/R) process for different period, both with or without CBX7 inhibitor or si-CBX7. The results showed that the expression of CBX7, GRP78, p-eIF2α and CHOP were increased after extension of I/R and H/R period. Moreover, overexpression of CBX7 could elevate the expression of CBX7, GRP78, p-eIF2α and CHOP. However, CBX7 inhibition with either UNC3866 or genetic knockdown lead to reduced expression of GRP78, p-eIF2α and CHOP through Nrf2/HO-1 activation in I/R and H/R injury. Furthermore, ML385, the Nrf2 inhibitor, could elevate endoplasmic reticulum stress level, abrogating the protective effects of UNC3866 against renal I/R injury. In conclusion, our results demonstrated that CBX7 inhibition alleviated AKI by preventing endoplasmic reticulum stress via Nrf2/HO-1 pathway, indicating that CBX7 inhibitor could be a potential therapeutic target for renal I/R injury.