Sato Asuka, Omichi Ryotaro, Maeda Yukihide, Ando Mizuo
Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata, Kita-Ku, Okayama, 700-8558, Japan.
Department of Otolaryngology and Neuro-Otology, Saitama Medical University, Faculty of Medicine, Morohongo 38, Moroyamamachi, Iruma-gun, Saitama, 350-0495, Japan.
Sci Rep. 2025 Mar 3;15(1):7506. doi: 10.1038/s41598-025-92400-2.
FKBP5 is a 51-Da FK506-binding protein and member of the immunophilin family involved in controlling the signaling of glucocorticoid receptor from the cytosol to nucleus. Fkbp5 has previously been shown to be expressed in murine cochlear tissue, including the organ of Corti (i.e., the sensory epithelium of the cochlea). Fkbp5 mice as used in this study show hearing loss in the low-frequency (8-kHz) range and click-evoked auditory brainstem response (ABR) threshold compared to wild-type mice. Both Fkbp5 and wild-type mice showed hearing loss at all frequencies and click-ABR thresholds at 24 h and 14 days following acoustic overexposure (AO). Tissues of the organ of Corti were subjected to RNA sequencing and KEGG pathway analysis. In Fkbp5 mice before AO, the mitogen-activated protein kinase (MAPK) signaling pathway was dysregulated compared to wild-type mice. In wild-type mice at 12 h following AO, the most significantly modulated KEGG pathway was the TNF signaling pathway and major MAPK molecules p38 and Jun were involved in the TNF signaling pathway. In Fkbp5 mice at 12 h following AO, the MAPK signaling pathway was dysregulated compared to wild-type mice following AO. In conclusion, Fkbp5 interacts with MAPK signaling in the organ of Corti in mice cochleae.
FKBP5是一种51千道尔顿的FK506结合蛋白，属于免疫亲和素家族成员，参与控制糖皮质激素受体从细胞质到细胞核的信号传导。先前已证明Fkbp5在小鼠耳蜗组织中表达，包括柯蒂氏器（即耳蜗的感觉上皮）。本研究中使用的Fkbp5小鼠与野生型小鼠相比，在低频（8千赫）范围内存在听力损失，并且短声诱发的听觉脑干反应（ABR）阈值升高。在声过度暴露（AO）后24小时和14天时，Fkbp5小鼠和野生型小鼠在所有频率下均出现听力损失，且短声ABR阈值升高。对柯蒂氏器组织进行RNA测序和KEGG通路分析。在AO之前，与野生型小鼠相比，Fkbp5小鼠的丝裂原活化蛋白激酶（MAPK）信号通路失调。在AO后12小时的野生型小鼠中，最显著调节的KEGG通路是TNF信号通路，主要的MAPK分子p38和Jun参与了TNF信号通路。在AO后12小时的Fkbp5小鼠中，与AO后的野生型小鼠相比，MAPK信号通路失调。总之，Fkbp5与小鼠耳蜗柯蒂氏器中的MAPK信号相互作用。
