Regulation of Hippo/YAP signaling pathway ameliorates cochlear hair cell injury by regulating ferroptosis

被引:8
作者
Niu, Xiaorong [1 ]
Han, Peng [1 ]
Liu, Junsong [1 ]
Chen, Zichen [2 ]
Ma, Xiaoyan [1 ]
Zhang, Ting [1 ]
Li, Baiya [1 ]
Ma, Xudong [3 ,4 ]
机构
[1] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Otorhinolaryngol Head & Neck Surg, Xian 710061, Shaanxi, Peoples R China
[2] Xi An Jiao Tong Univ, Affiliated Hosp 2, Dept Otorhinolaryngol Head & Neck Surg, Xian 710004, Shaanxi, Peoples R China
[3] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Neurosurg, Xian 710061, Shaanxi, Peoples R China
[4] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Neurosurg, 227 Yanta West Rd, Xian 710061, Shaanxi, Peoples R China
关键词
YAP; Cochlear hair cell; Ferroptosis; Transferrin receptor; Ferritin light chain; CISPLATIN-INDUCED OTOTOXICITY; AUTOPHAGY; VERTEPORFIN; SENSITIVITY; EXPRESSION; TRANSPORT; DEATH;
D O I
10.1016/j.tice.2023.102051
中图分类号
R602 [外科病理学、解剖学]; R32 [人体形态学];
学科分类号
100101 ;
摘要
Cisplatin, which is effective for the treatment of solid tumors, also can induce cochlear hair cell damage. Therefore, this study was intended to explore how Hippo/YAP signaling pathway affects the cochlear hair cell injury by regulating ferroptosis. After cisplatin induction, or LAT1-IN-1 (YAP activator) and verteporfin (YAP inhibitor) treatment or transfection, the viability of HEI-OC1 cells was detected by cell counting kit-8 (CCK-8) assay. The iron level and the levels of oxidative stress markers (ROS, MDA and 4-HNE) were analyzed by iron assay kit, reactive oxygen species (ROS), malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) assay kits, respectively. The expression of ferritin light chain (FTL) in HEI-OC1 cells was detected by immunofluorescence and protein expressions of yes associated protein (YAP,) phosphorylated YAP (p-YAP), transferrin receptor (TFRC), glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4) and solute carrier family 7 member 11 (SLC7A11) in HEI-OC1 cells were detected by western blot. The transcription of FTL and TFRC by YAP1 was verified by dual-luciferase reporter assay. The transfection efficiency of small interfering RNA (si-RNA) specific to FTL (siRNA-FTL) and TFRC (siRNA-TFRC) was confirmed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). As a result, cisplatin inhibited the viability of HEIOC1 cells by increasing free Fe2+ level and decreasing FTL level. LAT1-IN-1 promoted the viability of cisplatininduced HEI-OC1 cells by suppressing oxidative stress level, free Fe2+ level, ferroptosis and increasing FTL level, while the effect of verteporfin was the opposite. YAP1 transcriptionally regulated the expression of FTL and TFRC. Inhibition of FTL suppressed the viability of cisplatin-induced HEI-OC1 cells by increasing oxidative stress level, free Fe2+ level, ferroptosis and decreasing FTL level, while the effect of TFRC inhibition was the opposite. In conclusion, YAP1 ameliorated cochlear hair cell injury by upregulating FTL and TFRC to suppress ferroptosis.
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页数:10
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