SerpinA3K Deficiency Reduces Oxidative Stress in Acute Kidney Injury

Abstract

We previously showed that SerpinA3K is present in urine from rats and humans with acute kidney injury (AKI) and chronic kidney disease (CKD). However, the specific role of SerpinA3K during renal pathophysiology is unknown. To begin to understand the role of SerpinA3K on AKI, SerpinA3K-deficient (KOSA3) mice were studied 24 h after inducing ischemia/reperfusion (I/R) and compared to wild type (WT) mice. Four groups were studied: WT+S, WT+IR, KOSA3+S, and KOSA3+IR. As expected, I/R increased serum creatinine and BUN, with a GFR reduction in both genotypes; however, renal dysfunction was ameliorated in the KOSA3+IR group. Interestingly, the increase in UH2O2 induced by I/R was not equally seen in the KOSA3+IR group, an effect that was associated with the preservation of antioxidant enzymes’ mRNA levels. Additionally, FOXO3 expression was initially greater in the KOSA3 than in the WT group. Moreover, the increase in BAX protein level and the decrease in Hif1a and Vegfa induced by I/R were not observed in the KOSA3+IR group, suggesting that these animals have better cellular responses to hypoxic injury. Our findings suggest that SerpinA3K is involved in the renal oxidant response, HIF1α/VEGF pathway, and cell apoptosis.

From Acute to Chronic: Unraveling the Pathophysiological Mechanisms of the Progression from Acute Kidney Injury to Acute Kidney Disease to Chronic Kidney Disease

“…On the contrary, some authors have found that under hypoxia conditions HIF-1α binds to FoxO3, which is thought to be a renoprotection factor after AKI, and subsequently inhibits the hydroxylation and degradation of FoxO3 [103]. SerpinA3K is another novel biomarker for the AKI to CKD transition in animal models, and knockout of serpinA3K resulted in higher FoxO3 expression with improved cellular responses to hypoxic injury, suggesting SerpinA3K's involvement in the renal oxidant response, HIF1α pathway, and cell apoptosis [104,105]. Studies exploring the effectiveness of PHD inhibitors in renal injury highlighted the positive impact of HIFs on renal fibrosis [106].…”