Overexpression of aquaporin 2 in renal tubular epithelial cells alleviates pyroptosis

BACKGROUND: Severe renal ischemia-reperfusion injury results in worse outcomes of kidney transplantation. Compared to the collecting duct, the proximal tubule is more likely to exhibit severe pyroptosis and damage during renal ischemia-reperfusion. Aquaporins were reported of having regulatory roles in pyroptosis. We explored whether aquaporin 2 overexpression in proximal tubular cells could alleviate ischemia-reperfusion injury related pyroptosis. METHODS: A renal ischemia-reperfusion model of mice was established, and human kidney 2 cells were treated with hypoxia-reoxygenation. Aquaporin 2 overexpression was achieved in human kidney 2 cells transfected with lentivirus, which were then cultured with murine cells. Renal tissues and serum of the mice, and human kidney 2 cells were subjected to histological, molecular, and biochemical examinations. RESULTS: Compared with the sham group, the renal function of the ischemia-reperfusion group was significantly decreased, and the tissue injury was severe and accompanied by more nuclear dissolved and necrosis. Besides, the expression of aquaporin 1-5 decreased significantly, while the expression of Toll-like receptor 4, caspase-1, kim-1 and interleukin 1β and 18 increased significantly in ischemia-reperfusion group. Similar results were observed in the human kidney 2 cells test. Overexpression of aquaporin 2 partially reversed the cell damage, pyroptosis, and molecular expression changes of human kidney 2 cells induced by hypoxia-reoxygenation. CONCLUSIONS: Our findings suggest that aquaporin 2 overexpression can potentially reduce pyroptosis in proximal tubular cells, and thus might be a novel target for relieving pyroptosis and injury in renal ischemia-reperfusion injury.