Overexpression of Aquaporin 2 in Renal Tubular Epithelial Cells Alleviates Pyroptosis
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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.
Tarawneh N, Hamadneh L, Alshaer W, Al Bawab A, Bustanji Y, Abdalla S Heliyon. 2024; 10(20):e39402.
PMID: 39498081 PMC: 11532241. DOI: 10.1016/j.heliyon.2024.e39402.
Kan H, Zhao M, Wang W, Sun B Mol Biotechnol. 2024; 67(3):1165-1177.
PMID: 38498283 DOI: 10.1007/s12033-024-01116-7.
Tarawneh N, Hamadneh L, Abu-Irmaileh B, Shraideh Z, Bustanji Y, Abdalla S Molecules. 2023; 28(9).
PMID: 37175233 PMC: 10180100. DOI: 10.3390/molecules28093823.
Qiu Z, Jiang T, Li Y, Wang W, Yang B Adv Exp Med Biol. 2023; 1398:155-177.
PMID: 36717493 DOI: 10.1007/978-981-19-7415-1_11.
Pyroptosis: A Newly Discovered Therapeutic Target for Ischemia-Reperfusion Injury.
Zheng Y, Xu X, Chi F, Cong N Biomolecules. 2022; 12(11).
PMID: 36358975 PMC: 9687982. DOI: 10.3390/biom12111625.