Phosphatase and tensin homolog deleted on chromosome 10 contributes to phenotype transformation of fibroblasts in idiopathic pulmonary fibrosis via multiple pathways

Jing Geng; Xiaoxi Huang; Ying Li; Xuefeng Xu; Shuhong Li; Dingyuan Jiang; Zheng Liu; Huaping Dai

doi:10.1177/1535370215600100

Phosphatase and tensin homolog deleted on chromosome 10 contributes to phenotype transformation of fibroblasts in idiopathic pulmonary fibrosis via multiple pathways

Exp Biol Med (Maywood). 2016 Jan;241(2):157-65. doi: 10.1177/1535370215600100. Epub 2015 Aug 11.

Authors

Jing Geng¹, Xiaoxi Huang², Ying Li², Xuefeng Xu³, Shuhong Li¹, Dingyuan Jiang¹, Zheng Liu², Huaping Dai⁴

Affiliations

¹ Department of Respiratory and Critical Care Medicine, Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Beijing Chao-Yang Hospital-Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing 100020, P.R. China.
² Department of Medical Research, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
³ Department of Respiratory and Critical Care Medicine, Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Beijing Chao-Yang Hospital-Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing 100020, P.R. China National Clinical Research Centre for Respiratory Medicine, Beijing Hospital, Beijing 100730, P.R. China.
⁴ Department of Respiratory and Critical Care Medicine, Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Beijing Chao-Yang Hospital-Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing 100020, P.R. China daihuaping@ccmu.edu.cn.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease and considered as a cancer-like disease. The phosphatase and tensin homologue deleted on chromosome 10 (PTEN) tumor suppressor has drawn attention in the pathogenesis of IPF. However, the role of PTEN in phenotypic transformation of lung fibroblasts, particularly in the migratory and invasive phenotype, is still elusive. Our data showed that PTEN expression was markedly reduced in both fibroblasts and myofibroblasts from IPF patients. Furthermore, loss of PTEN led to the transformation of normal fibroblasts to myofibroblasts and increased proliferation, apoptosis resistance, and migration/invasion activities. PTEN deficiency upregulated hyaluronan synthase 2 expression and thereby enhanced the invasion ability of fibroblasts. Cross-talk between PTEN and the transforming growth factor β1 (TGF-β1) pathway and PTEN reduction by hypoxia were observed. These findings suggest that PTEN is implicated in multiple pathways and plays a crucial role in the pathogenesis of IPF.

Keywords: Fibroblasts; idiopathic pulmonary fibrosis; phenotype transformation; phosphatase and tensin homologue deleted on chromosome 10.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Cell Movement
Cell Proliferation
Cell Transformation, Neoplastic*
Fibroblasts / physiology*
Glucuronosyltransferase / analysis
Humans
Hyaluronan Synthases
Idiopathic Pulmonary Fibrosis / pathology*
Lung / pathology*
Male
Middle Aged
PTEN Phosphohydrolase / metabolism*
Transforming Growth Factor beta1 / metabolism

Substances

Transforming Growth Factor beta1
Glucuronosyltransferase
HAS2 protein, human
Hyaluronan Synthases
PTEN Phosphohydrolase
PTEN protein, human