HEI-OC1 auditory cell line as a cellular model to understand hearing loss due to IGF-1 deficiency

Resumen del póster presentado al 42nd Congress of the Spanish Society of Biochemistry and Molecular Biology (SEBBM), celebrado en Madrid del 16 al 19 de julio de 2019.Hearing loss is the most common sensory deficit in the human population. Mutations in the gene coding for IGF-1 cause sensorineural hearing loss in man and mice. Actions of IGF-1 are mediated by binding to its high affinity transmembrane receptor, IGF1R. This interaction typically leads to the activation of the PI3K-AKT pathway and of the MAPK-ERK cascade. To gain insight into the molecular mechanisms involved in IGF-1 downstream signaling in the sensory hair cells, we have used HEI-OC1 (House Ear Institute-Organ of Corti 1), a cell line derived from the auditory organ of the transgenic ImmortomouseTMat postnatal day 7. The study of the relative expression of genes of the IGF system by RT-qPCR showed that IGF system factors and receptors are expressed in HEI-OC1 and that Igf1 transcripts are more abundant than those of Igf2 and Ins1/ 2. We also studied the cellular actions and downstream signaling pathways of IGF-1. Cell cycle and apoptosis were studied by flow cytometry and immunohistochemistry, whilst activation of target proteins was measured by Western blotting. The consequences of blockage of IGF-1 actions were analyzed by using specific IGF1R inhibitors and XTT assay. IGF-1 increased survival, proliferation, as well as glucose metabolism and protein synthesis, whereas autophagic flux was decreased and apoptosis inhibited. In conclusion, HEI-OC1 cells can be used as a model to understand the actions of IGF-1 in hair cells, to identify novel targets and to unravel the molecular mechanisms involved in IGF-1 deficiency-associated otic damage.This work was supported by the Spanish Ministerio de Economía y Competitividad (MINECO)/FEDER SAF2017-86107-R. AGM holds a MECD FPU16/03308 fellowship.Peer reviewe