Abstract
Renal ischemia-reperfusion (I/R) can induce oxidative stress and injury via the generation of reactive oxygen species (ROS). Renal proximal tubular cells are susceptible to oxidative stress, and the dysregulation of renal proximal tubular cellular homeostasis can damage cells via apoptotic pathways. A recent study showed that the generation of ROS can increase perilipin 2 (Plin2) expression in HepG2 cells. Some evidence has also demonstrated the association between Plin2 expression and renal tumors. However, the underlying mechanism of Plin2 in I/R-induced acute kidney injury (AKI) remains elusive. Here, using a mouse model of I/R-induced AKI, we found that ROS generation was increased and the expression of Plin2 was significantly upregulated. An in vitro study further revealed that the expression of Plin2, and the generation of ROS were significantly upregulated in primary tubular cells treated with hydrogen peroxide. Accordingly, Plin2 knockdown decreased apoptosis in renal proximal tubular epithelial cells treated with hydrogen peroxide, which depended on the activation of peroxisome proliferator-activated receptor α (PPARα). Overall, the present study demonstrated that Plin2 is involved in AKI; knockdown of this marker might limit apoptosis via the activation of PPARα. Consequently, the downregulation of Plin2 could be a novel therapeutic strategy for AKI.
Highlights
Acute kidney injury (AKI) is a problem associated with rapid renal dysfunction and high mortality [1], which is often caused by renal ischemia-reperfusion (I/R) in clinics
We determined the relationship between perilipin 2 (Plin2) and peroxisome proliferator-activated receptor α (PPARα) in the regulation of apoptosis in a model of AKI induced by I/R (Figure 5)
Renal I/R injury (IRI) resulted in the upregulation of Plin2, which inhibited PPARα expression and increased mitochondrial reactive oxygen species (ROS) production, leading to cell apoptosis and AKI
Summary
Acute kidney injury (AKI) is a problem associated with rapid renal dysfunction and high mortality [1], which is often caused by renal ischemia-reperfusion (I/R) in clinics. Renal I/R injury (IRI) is characterized by the restriction of blood supply to the kidney followed by the restoration of blood flow. I/R can induce oxidative stress and injure organs via the generation of reactive oxygen species (ROS). In IRI, the production of ROS remains high for 24 h after reperfusion [2]. It was found that renal proximal tubular cells are susceptible to this oxidative stress. The dysregulation of renal proximal tubular cellular homeostasis can damage cells via apoptotic pathways [3,4,5]. Managing ROS is an important target for the prevention and treatment of AKI
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