Role of prostaglandin E2 receptor 4 in the modulation of apoptosis and mitophagy during ischemia/reperfusion injury in the kidney

The mechanisms by which prostaglandin E2 receptor 4 (EP4) protects against renal ischemia-reperfusion (I/R) injury (IRI) remain to be fully elucidated. In the present study, the protective effects of EP4 signaling on renal mitochondria and against renal IRI, as well as the underlying mechanisms, were investigated. A rat model of renal IRI was established. The right kidney was separated without damaging the artery clip, and the renal blood perfusion was then restored after 60 min. One group of animals was treated with EP4 agonists prior to I/R. The mitochondrial mass, the copy number of mitochondrial (mt)DNA, adenosine triphosphate (ATP) production and mitochondrial autophagy were analyzed. It was identified that renal IRI reduced the mitochondrial mass, decreased the mtDNA copy number and inhibited ATP production. The loss of renal mitochondria was attributed to the excessive mitochondrial autophagy induced by renal IRI. Pre-treatment with EP4 agonist inhibited excessive mitochondrial autophagy, the loss of mitochondria and maintained and the energy imbalance within the cells. It was indicated that renal IRI causes excessive mitochondrial autophagy, which is one of the important causes of renal dysfunction.