BUSCADOR RECOLECTA

Insulin-like growth factor 1 (IGF-1) is a trophic factor for the nervous system where it exerts pleiotropic effects, including the regulation of metabolic homeostasis. IGF-1 deficiency induces morphological alterations in the cochlea, apoptosis and hearing loss. While multiple studies have addressed the role of IGF-1 in hearing protection, its potential function in the modulation of otic metabolism remains unclear. Here, we report that “House Ear Institute-organ of Corti 1” (HEI-OC1) auditory cells express IGF-system genes that are regulated during their differentiation. Upon binding to its high-affinity receptor IGF1R, IGF-1 activates AKT and mTOR signaling to stimulate anabolism and, concomitantly, to reduce autophagic catabolism in HEI-OC1 progenitor cells. Notably, IGF-1 stimulation during HEI-OC1 differentiation to mature otic cells sustained both constructive metabolism and autophagic flux, possibly to favor cell remodeling. IGF1R engagement and downstream AKT signaling promoted HEI-OC1 cell survival by maintaining redox balance, even when cells were challenged with the ototoxic agent cisplatin. Our findings establish that IGF-1 not only serves an important function in otic metabolic homeostasis but also activates antioxidant defense mechanisms to promote hair cell survival during the stress response to insults., This research was funded by Spanish MCIN/AEI/10.13039/501100011033 THEARPYPID2020-115274RB-I00; 0551_PSL_6_E POCTEP FGCSIC/ PSL-INTERREG/FEDER NITROPROHEAR and CA20121 COST Action/EU—BenBedPhar grants to I.V.-N. Á.G.-M. holds an FPU (FPU16/03308; MECD) fellowship, and L.R.-d.l.R. holds a CIBER ISCIII researcher contract., Peer reviewed