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

- MIF was downregulated in PVM/Ms from stria vascularis of lateral wall of cochlear in aged mice.
- The viability of PVM/Ms was decreased and the apoptotic PVM/Ms number was markedly increased in aged mice.
- MIF affects the viability and apoptosis of PVM/Ms in vitro.
- MIF knockdown inhibited the viability and induced apoptosis of PVM/Ms from young mice.
- MIF overexpression induced the viability and inhibited apoptosis of PVM/Ms from aged mice.

Macrophage migration inhibitory factor (MIF) plays an important role in hearing function; however, the underlying mechanism remains indistinct. PVM/Ms from the stria vascularis of lateral wall of cochlea in young and aged mice were isolated, and the mRNA and protein expression levels were detected. MIF was knocked down or overexpresssed in vitro, and transfection was performed in vivo. Cell viability and apoptosis were determined by MTT assay and flow cytometry analysis, respectively. The hearing ability was tested by the auditory brain stem response. The results showed that MIF expression was significantly downregulated in aged mice. In aged mice, the viability of PVM/Ms significantly decreased, but the apoptotic number markedly increased. MIF knockdown in PVM/Ms in vitro significantly inhibited cell viability and induced cell apoptosis, but MIF overexpression showed contrasting results. Further studies showed that MIF knockdown in young mice resulted in serious hearing loss, but MIF overexpression in aged mice restored the hearing. Si-MIF inhibited the viability and induced apoptosis of PVM/Ms from young mice, whereas Ad-MIF induced the viability and inhibited apoptosis of PVM/Ms from aged mice. Moreover, MIF effectively altered the expression levels of CDK1, BRAF, p-ERK1/2, p-PI3K, and p-Akt. Furthermore, ERK inhibitor PD98059 or PI3K inhibitor LY294002 significantly reversed the effects of Si-MIF on PVM/Ms from young mice, whereas ERK activator EGF or PI3K activator IGF significantly reversed the effects of Ad-MIF on PVM/Ms from aged mice. Taken together, MIF mediates the viability and apoptosis of PVM/Ms, at least partially, through MAPK and/or PI3K/Akt pathway.