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miR-34a/ATG9A/TFEB Signaling Modulates Autophagy in Cochlear Hair Cells and Correlates with Age-related Hearing Loss.
- Source :
-
Neuroscience . May2022, Vol. 491, p98-109. 12p. - Publication Year :
- 2022
-
Abstract
- • miR-34a inhibits TFEB nuclear translocation in HEI-OC1 cells. • TFEB interacts with ATG9A in HEI-OC1 cells. • Rapamycin attenuates AHL in C57BL/6 mice. Our previous studies revealed that miR-34a suppresses autophagy in the ageing cochlea, which correlates with cochlear hair cell loss and age-related hearing loss (AHL). However, the mechanisms underlying miR-34a regulation of autophagy in the cochlea remain unclear. Here, we show that nuclear translocation of transcription factor EB (TFEB), a master regulator of autophagy, was regulated by miR-34a in HEI-OC1 cells. Moreover, ATG9A, one of the main targets of miR-34a, was shown to interact with TFEB and thus promote its nuclear translocation in HEI-OC1 cells. Rapamycin rescued the inhibition of TFEB nuclear translocation induced by miR-34a/ATG9A activation, restored autophagic flux and consequently prevented HEI-OC1 cell death. Long-term supplementation with rapamycin attenuated outer hair cells (OHCs) and inner hair cell synaptic ribbons, and delayed AHL in C57BL/6 mice. Most importantly, rapamycin partially restored TFEB's nuclear localization and autophagic flux in OHCs of the ageing cochlea. These findings open new avenues for protection against AHL through miR-34a/ATG9a/TFEB modulation of autophagy. [ABSTRACT FROM AUTHOR]
- Subjects :
- *PRESBYCUSIS
*HAIR cells
*HEARING disorders
*AUTOPHAGY
*LABORATORY mice
*RAPAMYCIN
Subjects
Details
- Language :
- English
- ISSN :
- 03064522
- Volume :
- 491
- Database :
- Academic Search Index
- Journal :
- Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 157031449
- Full Text :
- https://doi.org/10.1016/j.neuroscience.2022.03.033