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

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.

PTEN gene silencing contributes to airway remodeling and induces airway smooth muscle cell proliferation in mice with allergic asthma

“…In addition, TGF-b-induced activation of fibroblasts into α-SMA-positive myofibroblasts in order to synthesize type-1 collagen is a vital event in allergic asthma (22). In line with our results, a prior study also observed that PTEN overexpression resulted in a reduced expression of α-SMA (25).…”

PTEN and α-SMA Expression and Diagnostic Role in Oral Submucous Fibrosis and Oral Squamous Cell Carcinoma with Concomitant Oral Submucous Fibrosis

“…According to Xie et al [50], PTEN overexpression decreases signalling via the PI3K/AKT and TGF β/Smad3 pathways in IPF and inhibits TGF β1 mediated myofibroblast differentiation. An increased TGF β in OSF can reduce PTEN levels allowing for AKT activity and consequently prolonged survival of fibroblasts and increased ECM production and fibrosis [21].…”

Matrix Metalloproteinases and Their Inhibitors in Pulmonary Fibrosis: EMMPRIN/CD147 Comes into Play

“…Although SLPI null animals with overexpressed MMP-2 expression show longer wound recovery and enhanced localized scarring, they do not develop PF [123]. The tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) inhibits the expression levels of several crucial proteins in TGF-β1-induced fibrosis, including MMP-2, MMP-9 and α-SMA by blocking the phosphatidylinositol 3-kinase/Akt and TGF-β1/SMAD3 pathways, reducing fibroblast-to-myofibroblast transition (FMT) [124].…”