Knockdown and mutation of Pou4f3 gene mutation promotes pyroptosis of cochleae in cisplatin-induced deafness mice by NLRP3/caspase-3/GSDME pathway

Objective: To investigate the effect and mechanism of Pou4f3 gene mutation on pyroptosis in cochleae of cisplatin-induced deafness mice. Methods: Mice were intraperitoneally injected with cisplatin to construct an animal model of deafness, and sh-Pou4f3 and mutant vector were injected to alter gene expression. TUNEL staining was used to assess the apoptosis level of cochlear hair cells, ELISA was used to detect the secretion of inflammatory factors, and immunofluorescence and Western Blot were used to detect the expression of pyroptosis related factors. Results: Cisplatin induced pyroptosis through NLRP3/Caspase-3/GSDME pathway and significantly down-regulated Pou4f3 level. Pou4f3 mutations promote cochlear hair cell pyroptosis by activating the NLRP3/Caspase-3/GSDME pathway. Knockdown of Pou4f3 can superimpose cisplatin treatment to induce pyroptosis of cochlear hair cells through NLRP3/Caspase-3/GSDME pathway. Conclusion: Pou4f3 gene mutation promotes pyroptosis of cochleae in cisplatin-induced deafness mice through NLRP3/Caspase-3/GSDME pathway.