Role of the PI3K/AKT pathway and PTEN in otitis media

Exp Cell Res. 2020 Feb 1;387(1):111758. doi: 10.1016/j.yexcr.2019.111758. Epub 2019 Dec 13.

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.

Keywords: Middle ear; Mucosal growth regulation; nontypeable Haemophilus influenza.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Female
  • Heterocyclic Compounds, 3-Ring / pharmacology
  • Humans
  • Hyperplasia / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mucous Membrane / drug effects
  • Mucous Membrane / metabolism
  • Otitis Media / drug therapy
  • Otitis Media / metabolism*
  • PTEN Phosphohydrolase / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Signal Transduction / physiology

Substances

  • Heterocyclic Compounds, 3-Ring
  • MK 2206
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • Pten protein, mouse
  • Pten protein, rat