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miR-130b-3p involved in the pathogenesis of age-related hearing loss via targeting PPARγ and autophagy.
- Source :
-
Hearing Research . Aug2024, Vol. 449, pN.PAG-N.PAG. 1p. - Publication Year :
- 2024
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Abstract
- • Findings indicate a direct binding between PPARγ and miR-130b-3p. • exogenous overexpression of miR-130 b-3 p resulted in the decrease of ATG5, Becline and LC3B II/I. • MiR-130b-3p/PPARγ contributed to the premature senescence of these H 2 O 2 -induced HEI-OC1 cells. The study focuses on the underlying regulatory mechanism of age-related hearing loss (ARHL), which results from autophagy dysregulation mediated by miR-130b-3p targeting PPARγ. We constructed miR-130b-3p knockout (antagomir) and PPARγ over-expression (OE-PPARγ) mice model by injecting mmu-miR-130b-3p antagomir and HBAAV2/Anc80-m-Pparg-T2A-mCHerry into the right ear' round window of each mouse, respectively. In vitro, we introduced oxidative stress within HEI-OC1 cells by H 2 O 2 and exogenously changed the miR-130b-3p and PPARγ levels. MiRNA level was detected by RT-qPCR, proteins by western blotting and immunohistochemistry. Morphology of autophagosomes was observed by electron microscopy. In vivo, the cochlea of aged mice showed higher miR-130b-3p expression and lower PPARγ expression, while exogenous inhibition of miR-130b-3p up-regulated PPARγ expression. Autophagy-related biomarkers expression (ATG5, Beclin-1 and LC3B II/I) decreased in aged mice, which reversely increased after the inhibition of miR-130b-3p. The elevation of PPARγ demonstrated similar effects. Contrarily, exogenous overexpression of miR-130b-3p resulted in the decrease of ATG5, Beclin-1 and LC3B II/I. We created oxidative stress within HEI-OC1 by H 2 O 2 , subsequently observed the formation of autophagosomes under electron microscope, so as the elevated cell apoptosis rate and weakened cell viability. MiR-130b-3p/PPARγ contributed to the premature senescence of these H 2 O 2 -induced HEI-OC1 cells. MiR-130b-3p regulated HEI-OC1 cell growth by targeting PPARγ, thus leading to ARHL. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03785955
- Volume :
- 449
- Database :
- Academic Search Index
- Journal :
- Hearing Research
- Publication Type :
- Academic Journal
- Accession number :
- 177755656
- Full Text :
- https://doi.org/10.1016/j.heares.2024.109029