Department of Otorhinolaryngology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Department of Otorhinolaryngology, Hebei Eye Hospital, Xingtai, Hebei, China.
PeerJ. 2022 Nov 1;10:e14267. doi: 10.7717/peerj.14267. eCollection 2022.
Age-related hearing loss is an increasing sensorineural hearing loss. But the pathogenesis of ARHL has not been clarified. Herein, we studied the role and significance of PIN1 in regulating autophagy activity in senescence HEI-OC1cells and HCs.
C57BL/6 mice and HEI-OC1 cells were contained in our research. Transfection of plasmids and juglone were used to upregulate or inhibit the PIN 1 expression. Immunofluorescence and Western blot were used to detect the expression of PIN1, LC3, p62, p21 and p16 protein levels in the hair cells of C57BL/6 mice cochleae and HEI-OC1 cells. Senescence-associated -galactosidase (SA--gal) staining was used to investigate the senescent level.The results of this study showed that the level of autophagy increased in the senescent auditory hair cells. When inhibited the autophagy level with 3-MA, the senescent HEI-OC1 cells were alleviated. The autophagy activity in senescent HEI-OC1 cells also could be reduced by overexpressing PIN1 protein. On the contrary, inhibiting PIN1 could increase the autophagy level of senescent cells and cochlear hair cells.
PIN1 might regulate autophagy activity to induce the senescent of HEI-OC1cells and HCs, which will provide a theoretical support for the prevention and treatment of age-related hearing loss.
年龄相关性听力损失是一种进行性感觉神经性听力损失。但 ARHL 的发病机制尚未阐明。在此，我们研究了 PIN1 在调节衰老的 HEI-OC1 细胞和 HC 中的自噬活性中的作用和意义。
本研究包含了 C57BL/6 小鼠和 HEI-OC1 细胞。转染质粒和 Juglone 用于上调或抑制 PIN1 的表达。免疫荧光和 Western blot 用于检测 C57BL/6 小鼠耳蜗毛细胞和 HEI-OC1 细胞中 PIN1、LC3、p62、p21 和 p16 蛋白水平的表达。衰老相关-β-半乳糖苷酶 (SA-β-gal) 染色用于检测衰老水平。本研究结果表明，衰老的听觉毛细胞中自噬水平增加。当用 3-MA 抑制自噬水平时，衰老的 HEI-OC1 细胞得到缓解。过表达 PIN1 蛋白也可以降低衰老 HEI-OC1 细胞的自噬活性。相反，抑制 PIN1 可以增加衰老细胞和耳蜗毛细胞的自噬水平。
PIN1 可能通过调节自噬活性诱导 HEI-OC1 细胞和 HC 的衰老，为防治年龄相关性听力损失提供理论依据。
