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.

Experimental Cell Research
|December 15, 2019
PubMed

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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