Suppression of the TGF-β signaling exacerbates degeneration of auditory neurons in kanamycin-induced ototoxicity in mice

被引：1
作者：
Nitta, Yoshihiro [1 ]
Kurioka, Takaomi [2 ]
Mogi, Sachiyo [1 ]
Sano, Hajime [3 ]
Yamashita, Taku [1 ]
机构：
[1] Kitasato Univ, Dept Otorhinolaryngol & Head & Neck Surg, Sch Med, 1-15-1 Kitasato,Minami ku, Sagamihara, Kanagawa 2520374, Japan
[2] Natl Def Med Coll, Dept Otorhinolaryngol, 3-2 Namiki, Tokorozawa, Saitama 3598513, Japan
[3] Kitasato Univ, Sch Allied Hlth Sci, Sagamihara, Kanagawa, Japan
来源：
SCIENTIFIC REPORTS | 2024年 / 14卷 / 01期
关键词：
Transforming growth factor-beta; Kanamycin; Ototoxicity; Spiral ganglion neuron; Cochlear inflammation; GROWTH-FACTOR-BETA; SPIRAL GANGLION NEURONS; AMINOGLYCOSIDE OTOTOXICITY; HAIR-CELLS; HEARING; GENTAMICIN; MECHANISMS; TGF-BETA-1;
D O I：
10.1038/s41598-024-61630-1
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Transforming growth factor-beta (TGF-beta) signaling plays a significant role in multiple biological processes, including inflammation, immunity, and cell death. However, its specific impact on the cochlea remains unclear. In this study, we aimed to investigate the effects of TGF-beta signaling suppression on auditory function and cochlear pathology in mice with kanamycin-induced ototoxicity. Kanamycin and furosemide (KM-FS) were systemically administered to 8-week-old C57/BL6 mice, followed by immediate topical application of a TGF-beta receptor inhibitor (TGF-beta RI) onto the round window membrane. Results showed significant TGF-beta receptor upregulation in spiral ganglion neurons (SGNs) after KM-FA ototoxicity, whereas expression levels in the TGF-beta RI treated group remained unchanged. Interestingly, despite no significant change in cochlear TGF-beta expression after KM-FS ototoxicity, TGF-beta RI treatment resulted in a significant decrease in TGF-beta signaling. Regarding auditory function, TGF-beta RI treatment offered no therapeutic effects on hearing thresholds and hair cell survival following KM-FS ototoxicity. However, SGN loss and macrophage infiltration were significantly increased with TGF-beta RI treatment. These results imply that inhibition of TGF-beta signaling after KM-FS ototoxicity promotes cochlear inflammation and SGN degeneration.
引用
收藏
页数：11
相关论文
共 50 条
[1]   Aminoglycoside ototoxicity and hair cell ablation in the adult gerbil: A simple model to study hair cell loss and regeneration [J].
Abbas, Leila ;
Rivolta, Marcelo N. .
HEARING RESEARCH, 2015, 325 :12-26
[2]   Near-infrared-light pre-treatment attenuates noise-induced hearing loss in mice [J].
Basta, Dietmar ;
Groeschel, Moritz ;
Struebing, Ira ;
Boyle, Patrick ;
Froehlich, Felix ;
Ernst, Arne ;
Seidl, Rainer .
PEERJ, 2020, 8
[3]   Mechanisms of disease:: Role of transforming growth factor β in human disease. [J].
Blobe, GC ;
Schiemann, WP ;
Lodish, HF .
NEW ENGLAND JOURNAL OF MEDICINE, 2000, 342 (18) :1350-1358
[4]   Inhibition of p38 Mitogen-Activated Protein Kinase Improves Nitric Oxide-Mediated Vasodilatation and Reduces Inflammation in Hypercholesterolemia [J].
Cheriyan, Joseph ;
Webb, Andrew J. ;
Sarov-Blat, Lea ;
Elkhawad, Maysoon ;
Wallace, Sharon M. L. ;
Maeki-Petaejae, Kaisa M. ;
Collier, David J. ;
Morgan, John ;
Fang, Zixing ;
Willette, Robert N. ;
Lepore, John J. ;
Cockcroft, John R. ;
Sprecher, Dennis L. ;
Wilkinson, Ian B. .
CIRCULATION, 2011, 123 (05) :515-523
[5]   Effect of statin on age-related hearing loss via drug repurposing [J].
Choo, Oak-Sung ;
Lee, Yun Yeong ;
Kim, Young Sun ;
Kim, Yeon Ju ;
Lee, Dong Ha ;
Kim, Hantai ;
Jang, Jeong Hun ;
Choung, Yun-Hoon .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2022, 1869 (11)
[6]   Semi-quantitative Determination of Protein Expression Using Immunohistochemistry Staining and Analysis: An Integrated Protocol [J].
Crowe, Alexandra R. ;
Yue, Wei .
BIO-PROTOCOL, 2019, 9 (24)
[7]   TGFβ biology in cancer progression and immunotherapy [J].
Derynck, Rik ;
Turley, Shannon J. ;
Akhurst, Rosemary J. .
NATURE REVIEWS CLINICAL ONCOLOGY, 2021, 18 (01) :9-34
[8]   TGF-β in progression of liver disease [J].
Dooley, Steven ;
ten Dijke, Peter .
CELL AND TISSUE RESEARCH, 2012, 347 (01) :245-256
[9]   Transforming growth factor- (TGF-)-induced up-regulation of TGF- receptors at the cell surface amplifies the TGF- response [J].
Duan, Dana ;
Derynck, Rik .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2019, 294 (21) :8490-8504
[10]   Targeted mutations of transforming growth factor-β genes reveal important roles in mouse development and adult homeostasis [J].
Dünker, N ;
Krieglstein, K .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 2000, 267 (24) :6982-6988
12345