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IGF-1 controls metabolic homeostasis and survival in HEI-OC1 auditory cells through AKT and mTOR signaling
- Publication Year :
- 2023
-
Abstract
- 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.
Details
- Database :
- OAIster
- Notes :
- Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Cooperation in Science and Technology, Instituto de Salud Carlos III, European Commission, García-Mato, Ángela, Cervantes, Blanca, Rodriguez-de la Rosa, Lourdes, Varela-Nieto, Isabel
- Publication Type :
- Electronic Resource
- Accession number :
- edsoai.on1373151397
- Document Type :
- Electronic Resource