Characterization of 3,3'-iminodipropionitrile (IDPN) damaged utricle transcriptome in the adult mouse utricle

Mengyao Tian; Jingyuan Huang; Hairong Xiao; Pei Jiang; Xiangyu Ma; Yanqin Lin; Xujun Tang; Yintao Wang; Mingchen Dai; Wei Tong; Zixuan Ye; Xia Sheng; Renjie Chai; Shasha Zhang

doi:10.3389/fnmol.2024.1487364

Characterization of 3,3'-iminodipropionitrile (IDPN) damaged utricle transcriptome in the adult mouse utricle

Front Mol Neurosci. 2024 Dec 23:17:1487364. doi: 10.3389/fnmol.2024.1487364. eCollection 2024.

Authors

Mengyao Tian^#^{1

2}, Jingyuan Huang^#^{1

2}, Hairong Xiao^#^{1

2}, Pei Jiang^#^{1

2}, Xiangyu Ma^{1

2}, Yanqin Lin^{1

2}, Xujun Tang^{1

2}, Yintao Wang^{1

2}, Mingchen Dai^{1

2}, Wei Tong^{1

2}, Zixuan Ye^{1

2}, Xia Sheng^{3

4}, Renjie Chai^{1

2

5

6

7

8}, Shasha Zhang^{1

2}

Affiliations

¹ State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, China.
² Southeast University, Shenzhen Research Institute, Shenzhen, China.
³ School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁴ Department of Environmental Health, School of Environmental Science and Engineering, Hainan University, Haikou, China.
⁵ Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.
⁶ Department of Otolaryngology Head and Neck Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
⁷ Institute for Stem Cell and Regeneration, Chinese Academy of Science, Beijing, China.
⁸ Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing, China.

^# Contributed equally.

Abstract

Utricle is an important vestibular sensory organ for maintaining balance. 3,3'-iminodipropionitrile (IDPN), a prototype nitrile toxin, has been reported to be neurotoxic and vestibulotoxic, and can be used to establish an in vivo damage model of vestibular dysfunction. However, the mechanism of utricular HCs damage caused by IDPN is unclear. Here, we first studied mice balance behavior and HCs damage in IDPN utricle damage model, and found that IDPN injection in vivo can cause vestibular dysfunction and HCs damage, which is more pronounced than neomycin damage model. Then we used RNA-seq to characterize the transcriptome of IDPN damaged utricle in detail to identify genes and pathways that play roles in this process. We found 1,165 upregulated genes and 1,043 downregulated genes in IDPN damaged utricles, and identified that NF-κB pathway and TNF pathway may play important roles in IDPN damage model. Our study provides details of transcriptome of IDPN utricle damage model for further study of vestibular dysfunction.

Keywords: IDPN; RNA-seq; hair cell damage; neomycin; utricle.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Key R&D Program of China (nos. 2022YFA0807000, 2023YFA1801804, 2021YFA1101300, 2021YFA1101800, and 2020YFA0112503), the Strategic Priority Research Program of the Chinese Academy of Science (XDA16010303), the National Natural Science Foundation of China (nos. 82171149, 82371166, 81970892, 82030029, 81970882, and 92149304), the Science and Technology Department of Sichuan Province (No. 2021YFS0371), the Shenzhen Science and Technology Program (JCYJ20230807114700001, JCYJ20190814093401920, and JCYJ20210324125608022), Guangdong Basic and Applied Basic Research Foundation (2024A1515010548), and the Open Research Fund of the State Key Laboratory of Genetic Engineering, Fudan University (no. SKLGE-2104).