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Updated: Jan 1, 2026

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
Role of the PI3K/AKT pathway and PTEN in otitis media
Hwan Ho Lee1, Anthony Chin1, Kwang Pak1
1Division of Otolaryngology, Department of Surgery, University of California, San Diego and San Diego VA Healthcare System, La Jolla, CA, 92093, USA.
Abstract:
Mucosal hyperplasia is common sequela of otitis media (OM), leading to the secretion of mucus and the recruitment of leukocytes. However, the pathogenic mechanisms underlying hyperplasia are not well defined. Here, we investigated the role of the AKT pathway in the development of middle mucosal hyperplasia using in vitro mucosal explants cultures and an in vivo rat model. The Akt inhibitor MK2206 treatment inhibited the growth of middle ear mucosal explants in a dose-dependent manner. In vivo, MK2206 also reduced mucosal hyperplasia. Unexpectedly, while PTEN is generally thought to act in opposition to AKT, the PTEN inhibitor BPV reduced mucosal explant growth in vitro. The results indicate that both AKT and PTEN are mediators of mucosal growth during OM, and could be potential therapeutic targets.
Insights
AKT and PTEN pathways regulate middle ear mucosal hyperplasia in otitis media (OM). Inhibiting AKT with MK2206 reduced hyperplasia, while PTEN inhibition also unexpectedly decreased growth, suggesting new therapeutic targets for OM.
Area of Science:
- Otolaryngology
- Molecular Biology
- Pathology
Background:
- Mucosal hyperplasia is a common consequence of otitis media (OM), characterized by mucus secretion and leukocyte infiltration.
- The precise molecular mechanisms driving middle ear mucosal hyperplasia in OM remain incompletely understood.
Purpose of the Study:
- To investigate the role of the AKT signaling pathway in the development of middle ear mucosal hyperplasia.
- To explore the involvement of PTEN, a known regulator of AKT, in this process.
Main Methods:
- Utilized in vitro cultures of middle ear mucosal explants.
- Employed an in vivo rat model of otitis media.
- Administered AKT inhibitor (MK2206) and PTEN inhibitor (BPV) to assess their effects on mucosal growth.
Main Results:
- MK2206 treatment demonstrated a dose-dependent inhibition of middle ear mucosal explant growth in vitro.
- In vivo administration of MK2206 significantly reduced mucosal hyperplasia in the rat model.
- Unexpectedly, the PTEN inhibitor BPV also reduced mucosal explant growth in vitro, contrary to its expected role.
Conclusions:
- Both AKT and PTEN signaling pathways are identified as key mediators of mucosal growth in the context of otitis media.
- These pathways represent potential therapeutic targets for managing mucosal hyperplasia associated with OM.
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