Macrophage migration inhibitory factor mediates viability and apoptosis of PVM/Ms through PI3K/Akt pathway

Area of Science:

• Otolaryngology
• Cell Biology
• Molecular Biology

Background:

• Macrophage migration inhibitory factor (MIF) is implicated in hearing, but its precise role and mechanisms are unclear.
• Age-related hearing impairment is a significant clinical concern, necessitating research into underlying cellular and molecular factors.

Purpose of the Study:

• To investigate the role of MIF in cochlear perivascular myeloid cells (PVM/Ms) and its impact on hearing function in young and aged mice.
• To elucidate the molecular pathways, including MAPK and PI3K/Akt, through which MIF influences PVM/Ms viability and apoptosis.

Main Methods:

• Isolation and analysis of PVM/Ms from young and aged mice to assess MIF expression.
• In vitro knockdown and overexpression of MIF in PVM/Ms, followed by assessments of cell viability and apoptosis.
• In vivo manipulation of MIF levels and auditory brainstem response testing to evaluate hearing ability.
• Analysis of signaling pathway components (CDK1, BRAF, ERK, PI3K, Akt) and use of pathway inhibitors/activators.

Main Results:

• MIF expression was significantly downregulated in aged mice, correlating with decreased PVM/Ms viability and increased apoptosis.
• MIF knockdown in young mice led to hearing loss, while MIF overexpression in aged mice improved hearing.
• MIF modulated the expression of key proteins in the MAPK and PI3K/Akt pathways, influencing PVM/Ms function.
• Pathway inhibitors and activators confirmed the involvement of MAPK and PI3K/Akt in mediating MIF's effects on PVM/Ms.

Conclusions:

• MIF plays a critical role in maintaining PVM/Ms viability and regulating apoptosis, thereby influencing hearing function.
• MIF exerts its effects, at least partially, through the MAPK and PI3K/Akt signaling pathways.
• Targeting MIF represents a potential therapeutic strategy for age-related hearing impairment.