PUBLICATION
Regulatory mechanisms of miR-96 and miR-184 abnormal expressions on otic vesicle development of zebrafish following exposure to β-diketone antibiotics
- Authors
- Li, J., Ling, Y., Huang, W., Sun, L., Li, Y., Wang, C., Zhang, Y., Wang, X., Dahlgren, R.A., Wang, H.
- ID
- ZDB-PUB-180929-9
- Date
- 2018
- Source
- Chemosphere 214: 228-238 (Journal)
- Registered Authors
- Keywords
- Hearing loss, Otic vesicle, Ototoxicity, miR-184, miR-96, β-Diketone antibiotics
- MeSH Terms
-
- Animals
- Anti-Bacterial Agents/toxicity*
- Embryonic Development
- Hair Cells, Auditory/drug effects
- Hearing Loss/chemically induced*
- Hearing Loss/genetics
- Ketones/toxicity
- Larva/drug effects
- MicroRNAs/genetics
- MicroRNAs/metabolism
- MicroRNAs/physiology*
- Otolithic Membrane/drug effects
- Otolithic Membrane/growth & development
- Zebrafish/embryology
- Zebrafish/growth & development
- PubMed
- 30265930 Full text @ Chemosphere
Citation
Li, J., Ling, Y., Huang, W., Sun, L., Li, Y., Wang, C., Zhang, Y., Wang, X., Dahlgren, R.A., Wang, H. (2018) Regulatory mechanisms of miR-96 and miR-184 abnormal expressions on otic vesicle development of zebrafish following exposure to β-diketone antibiotics. Chemosphere. 214:228-238.
Abstract
Chronic ototoxicity of β-diketone antibiotics (DKAs) to zebrafish (Danio rerio) was explored in detail by following abnormal expressions of two hearing-related miRNAs. Dose-dependent down-regulation of miR-96 and miR-184 was observed in otoliths during embryonic-larval development. Continuous DKA exposure to 120-hpf larva decreased sensitivity to acoustic stimulation. Development of otolith was delayed in treatment groups, showing unclear boundaries and vacuolization at 72-hpf, and utricular enlargement as well as decreased saccular volume in 96-hpf or latter larval otoliths. If one miRNA was knocked-down and another over-expressed, only a slight influence on morphological development of the otic vesicle occurred, but knocked-down or over-expressed miRNA both significantly affected zebrafish normal development. Injection of miR-96, miR-184 or both micRNA mimics to yolk sac resulted in marked improvement of otic vesicle phenotype. However, hair cell staining showed that only the injected miR-96 mimic restored hair cell numbers after DKA exposure, demonstrating that miR-96 played an important role in otic vesicle development and formation of hearing, while miR-184 was only involved in otic vesicle construction during embryonic development. These observations advance our understanding of hearing loss owing to acute antibiotic exposure and provide theoretical guidance for early intervention and gene therapy for drug-induced diseases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping