Downregulation of BST2 Rescues Cochlear Nerve Demyelination in Age-Related Hearing Loss via Enhancing Schwann Cell Migration.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41391004.
- Also identified by DOI 10.1111/acel.70325 and PMC identifier 12741203.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Cochlear nerve demyelination is a significant pathogenic factor of age-related hearing loss (ARHL), and Schwann cell (SC) migration function plays a key role in the maintenance and regeneration of myelin sheaths. Here, we found that bone marrow stromal antigen 2 (BST2) is significantly upregulated in cochlear SCs during aging following demyelination and hearing loss. However, specific knockdown of BST2 in SCs could obviously improve the SCs migration and the myelin sheath structure manifested in a reduction of E-cadherin expression and increased N-cadherin expression. Further mechanism analysis revealed that POU class 6 homeobox 1 (POU6F1) expression via the NF-κB pathwayleads to enhanced SCs migration ability and increased expression of the myelin protein zero (MPZ), thereby alleviating nerve demyelination and rescuing hearing loss. This study identifies BST2 as a novel therapeutic target for ARHL intervention. In conclusion, the specific downregulation of BST2 in cochlear SCs rescues age-related demyelination and hearing loss by activating the POU6F1/NF-κB pathway, thereby enhancing SC migration capacity and promoting MPZ expression.
Medical subject headings
- Schwann Cells
- Cell Movement
- Demyelinating Diseases
- Cochlear Nerve
- Hearing Loss
- Antigens, CD