Abstract
Background Pin1, as the peptidyl-prolyl isomerase, plays a vital role in cellular processes. However, whether it has a regulatory effect on renal ischemia and reperfusion (I/R) injury still remains unknown. Methods The hypoxia/reoxygenation (H/R) model in human kidney (HK-2) cells and the I/R model in rats were assessed to investigate the role of Pin1 on I/R-induced acute kidney injury. Male Sprague-Dawley rats were used to establish the I/R model for 15, 30, and 45 min ischemia and then 24 h reperfusion, with or without the Pin1 inhibitor, to demonstrate the role of Pin1 in acute kidney injury. HK-2 cells were cultured and experienced the H/R model to identify the molecular mechanisms involved. Results In this study, we found that Pin1 and oxidative stress were obviously increased after renal I/R. Inhibition of Pin1 with juglone decreased renal structural and functional injuries, as well as oxidative stress. Besides, Pin1 inhibition with the inhibitor, juglone, or the small interfering RNA showed significant reduction on oxidative stress markers caused by the H/R process in vitro. Furthermore, the results indicated that the expression of p38 MAPK was increased during H/R in vitro and Pin1 inhibition could reduce the increased expression of p38 MAPK. Conclusion Our results illustrated that Pin1 aggravated renal I/R injury via elevating oxidative stress through activation of the p38 MAPK pathway. These findings indicated that Pin1 might become the potential treatment for renal I/R injury.
Highlights
Acute kidney injury (AKI), which is characterized by fast deterioration of renal function, becomes a worldwide public issue with high incidence and mortality [1]
Pin1 were examined by RT-PCR and Western blot and the results showed that Pin1 mRNA and the protein level were continuing to increase as the extension of ischemic time, especially at 45 min ischemia (Figures 1(c)–1(e))
The results showed that Superoxide Dismutase (SOD) activity (Figure 1(f)) continued to decrease and MDA content (Figure 1(g)) continued to increase in the course of ischemia and reperfusion (I/R) progress, especially at 45 min ischemia
Summary
Acute kidney injury (AKI), which is characterized by fast deterioration of renal function, becomes a worldwide public issue with high incidence and mortality [1]. Previous research indicated that oxidative stress, characterized by rapid overproduction of reactive oxygen species (ROS), was considered one of the primary pathogeneses of I/R [4]. As the peptidyl-prolyl isomerase, plays a vital role in cellular processes Whether it has a regulatory effect on renal ischemia and reperfusion (I/R) injury still remains unknown. Our results illustrated that Pin aggravated renal I/R injury via elevating oxidative stress through activation of the p38 MAPK pathway. These findings indicated that Pin might become the potential treatment for renal I/R injury
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