Effects of the tumor suppressor PTEN on the pathogenesis of idiopathic pulmonary fibrosis in Chinese patients

Mol Med Rep. 2016 Mar;13(3):2715-23. doi: 10.3892/mmr.2016.4852. Epub 2016 Feb 3.

Abstract

Idiopathic pulmonary fibrosis (IPF) is characterized by progressive interstitial fibrosis, and is associated with a fatal outcome. The critical pathological mechanisms underlying IPF are largely unknown; however, accumulating evidence has indicated similarities between IPF and cancer. Therefore, the present study examined the expression levels of the tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in Chinese patients with IPF, using an enzyme‑linked immunosorbent assay. To determine the effects of PTEN on the development of pulmonary fibrosis, PTEN was overexpressed in transforming growth factor (TGF)‑β1‑treated human embryonic lung fibroblasts (HFL‑I cells). The serum levels of PTEN were significantly lower in 42 patients with IPF, as compared with in the healthy controls. In addition, PTEN overexpression enhanced apoptosis, and suppressed basal levels of proliferation and migration in fibroblasts. Notably, PTEN was able to specifically inhibit TGF‑β1‑induced proliferation and migration of the cells. Overexpression of PTEN also suppressed phosphorylation of Akt and Smad3, and decreased the expression levels of numerous proteins with critical roles in TGF‑β1‑induced fibrosis, including α‑smooth muscle actin, matrix metalloproteinase (MMP)‑2 and MMP‑9. These results indicated that PTEN may inhibit TGF‑β1‑mediated myofibroblast differentiation of fibroblasts by attenuating signaling via the phosphatidylinositol 3‑kinase/Akt and TGF‑β/Smad3 pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Apoptosis
  • Case-Control Studies
  • Cell Differentiation
  • Cell Line
  • Female
  • Fibroblasts / enzymology
  • Gene Expression
  • Humans
  • Idiopathic Pulmonary Fibrosis / blood*
  • Idiopathic Pulmonary Fibrosis / enzymology
  • Male
  • Middle Aged
  • PTEN Phosphohydrolase / blood*
  • PTEN Phosphohydrolase / genetics
  • Signal Transduction
  • Transforming Growth Factor beta1 / physiology

Substances

  • Transforming Growth Factor beta1
  • PTEN Phosphohydrolase
  • PTEN protein, human