Department of Otolaryngology and Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
J Tissue Eng Regen Med. 2020 Aug;14(8):1149-1156. doi: 10.1002/term.3089. Epub 2020 Jul 7.
Gentamicin-induced cochlear hair cell ototoxicity, such as oxidative stress and apoptosis, could be attenuated by mouse inner ear stem cells (IESCs). However, it is still unclear whether such protective effects could be mediated by exosomes derived from IESCs (IESCs-ex). In the present study, HEI-OC1 cells were exposed to gentamicin (2 mM) to establish an ototoxicity model and further treated with exosomes isolated from miR-182-5p transferred or non-transferred IESCs. IESCs-ex improved HEI-OC1 cell viability, as assayed by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide method, and alleviated the oxidative stress response induced by the gentamicin treatment, as confirmed by measuring the malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase levels. IESCs-ex increased relative miR-182-5p expression and decreased FOXO3 expression in the gentamicin-exposed HEI-OC1 cells. Furthermore, exosomes derived from miR-182-5p mimics that were pre-treated with IESCs could increase miR-182-5p and Bcl-2 expressions and decrease FOXO3 and Bax expressions in gentamicin-exposed HEI-OC1 cells. All of these results indicate that IESCs-ex could attenuate gentamicin-induced HEI-OC1 cell apoptosis and oxidative stress through the miR-182-5p/FOXO3 axis.
庆大霉素诱导的耳蜗毛细胞耳毒性，如氧化应激和细胞凋亡，可被小鼠内耳干细胞（IESCs）减弱。然而，尚不清楚这种保护作用是否可以通过 IESCs 衍生的外泌体（IESCs-ex）介导。在本研究中，用庆大霉素（2 mM）处理 HEI-OC1 细胞建立耳毒性模型，并用转染或未转染 miR-182-5p 的 IESCs 分离的外泌体进一步处理。通过 3-（4,5-二甲基-2-噻唑基）-2,5-二苯基四氮唑溴盐法测定，IESCs-ex 提高了 HEI-OC1 细胞活力，并通过测量丙二醛、超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶水平证实了其减轻庆大霉素处理引起的氧化应激反应。IESCs-ex 增加了庆大霉素暴露的 HEI-OC1 细胞中相对 miR-182-5p 的表达，并降低了 FOXO3 的表达。此外，用 IESCs 预处理的 miR-182-5p 模拟物衍生的外泌体可增加 miR-182-5p 和 Bcl-2 的表达，并降低庆大霉素暴露的 HEI-OC1 细胞中 FOXO3 和 Bax 的表达。所有这些结果表明，IESCs-ex 可通过 miR-182-5p/FOXO3 轴减轻庆大霉素诱导的 HEI-OC1 细胞凋亡和氧化应激。
