Exogenous induction of unphosphorylated PTEN reduces TGFβ-induced extracellular matrix expressions in lung fibroblasts

Motohiro Kimura, Naozumi Hashimoto, Masaaki Kusunose, Daisuke Aoyama, Koji Sakamoto, Shinichi Miyazaki, Akira Ando, Norihiro Omote, Kazuyoshi Imaizumi, Tsutomu Kawabe, Yoshinori Hasegawa

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Transforming growth factor β (TGFβ) plays an important role in regulating aberrant extracellular matrix (ECM) production from alveolar/epithelial cells (AECs) and fibroblasts in pulmonary fibrosis. Although the tumor suppressor gene phosphatase and tensin homologue deleted from chromosome 10 (PTEN) can negatively control many TGFβ-activated signaling pathways via the phosphatase activity, hyperactivation of the TGFβ-related signaling pathways is often observed in fibrosis. Loss of PTEN expression might cause TGFβ-induced ECM production. In addition, TGFβ was recently shown to induce loss of PTEN enzymatic activity by phosphorylating the PTEN C-terminus. Therefore, we hypothesized that exogenous transfer of unphosphorylated PTEN (PTEN4A) might lead to reduce TGFβ-induced ECM expression in not only epithelial cells but also fibroblasts. Adenovirus-based exogenous PTEN4A induction successfully reduced TGFβ-induced fibronectin expression and retained β-catenin at the cell membrane in human epithelial cells. Exogenous unphosphorylated PTEN also attenuated TGFβ-induced ECM production and inhibited TGFβ-induced β-catenin translocation in a human fibroblast cell line and in mouse primary isolated lung fibroblasts. Conversely, TGFβ-induced α-smooth muscle actin expression did not seem to be inhibited in these fibroblasts. Our data suggest that exogenous administration of unphosphorylated PTEN might be a promising strategy to restore TGFβ-induced loss of PTEN activity and reduce aberrant TGFβ-induced ECM production from epithelial cells and fibroblasts in lung fibrosis as compared with wild-type PTEN induction.

Original languageEnglish
Pages (from-to)86-97
Number of pages12
JournalWound Repair and Regeneration
Issue number1
Publication statusPublished - 01-01-2017

All Science Journal Classification (ASJC) codes

  • Surgery
  • Dermatology


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