Macrophage migration inhibitory factor knockdown inhibit viability and induce apoptosis of PVM/Ms
Wenjing Zhang1, Jian Zheng1, Juan Meng1
1Department of Otology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China.
Abstract:
Previous studies have suggested that macrophage migration inhibitory factor (MIF) serves an important role in hearing function; however, the underlying mechanism remains unclear. In the present study, perivascular‑resident macrophage‑like melanocytes (PVM/Ms) from the stria vascularis of the lateral cochlear wall in young and aged mice were isolated. The mRNA and protein expression levels of MIF were determined using reverse transcription‑quantitative polymerase chain reaction analysis, and western blotting, respectively. MIF expression was knocked down in vitro and in vivo using small interfering RNA. Cell viability was determined using an MTT assay and cell apoptosis was determined using flow cytometry analysis. The hearing ability was assessed through the auditory brain stem response in vivo. The results of the current study demonstrated that the expression of MIF was significantly downregulated in aged mice compared with in young mice. Furthermore, the viability of PVM/Ms in aged mice was significantly decreased and the number of apoptotic PVM/Ms was significantly increased compared with that in young mice. Further studies demonstrated that the MIF knockdown accentuated hearing loss in young mice as compared with the scramble control group. In addition, the MIF knockdown in PVM/Ms significantly inhibited cell viability and lead to a significant increase in the apoptotic cell number as compared with the control group. In summary, these results revealed that the MIF knockdown significantly accentuates hearing loss in young mice in vivo, and significantly inhibits the viability and induces the apoptosis of PVM/Ms in vitro. Thus, the results of the present study may provide a novel potential therapeutic approach and prevention method for presbycusis.
Insights
Macrophage migration inhibitory factor (MIF) is crucial for hearing. Reduced MIF expression in aged mice worsens hearing loss and cell death, suggesting MIF as a therapeutic target for age-related hearing impairment.
Area of Science:
- Otolaryngology
- Immunology
- Cell Biology
Background:
- Macrophage migration inhibitory factor (MIF) is implicated in hearing function, but its precise role and mechanism are not fully understood.
- Age-related hearing loss (presbycusis) is a growing concern, necessitating research into its underlying cellular and molecular mechanisms.
Purpose of the Study:
- To investigate the role of MIF in the stria vascularis and its impact on hearing function in young versus aged mice.
- To explore the effects of MIF knockdown on cochlear cell viability, apoptosis, and hearing ability.
Main Methods:
- Isolation of perivascular-resident macrophage-like melanocytes (PVM/Ms) from mouse cochlear stria vascularis.
- Quantification of MIF mRNA and protein expression using RT-qPCR and Western blotting.
- In vitro and in vivo knockdown of MIF using small interfering RNA (siRNA), followed by assessments of cell viability (MTT assay), apoptosis (flow cytometry), and hearing function (auditory brainstem response).
Main Results:
- MIF expression was significantly downregulated in aged mice compared to young mice.
- Aged mice exhibited decreased PVM/Ms viability and increased apoptosis.
- MIF knockdown exacerbated hearing loss in young mice and reduced PVM/Ms viability while increasing apoptosis in vitro.
Conclusions:
- MIF plays a protective role in maintaining hearing function and cochlear cell viability.
- MIF knockdown accentuates hearing loss and induces PVM/Ms apoptosis, highlighting MIF's potential as a therapeutic target for presbycusis.
