Phosphatase and tensin homolog deleted on chromosome 10 contributes to phenotype transformation of fibroblasts in idiopathic pulmonary fibrosis via multiple pathways.
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.
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.
Jing
J
Geng
Department of Medical Research, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
Xiaoxi
X
Huang
Department of Medical Research, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
Ying
Y
Li
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.
Xuefeng
X
Xu
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.
Shuhong
S
Li
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.
Dingyuan
D
Jiang
Department of Medical Research, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
Zheng
Z
Liu
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.
Huaping
H
Dai
D000328:Adult; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D005347:Fibroblasts / Q000502:physiology*; D014453:Glucuronosyltransferase / Q000032:analysis; D006801:Humans; D000076002:Hyaluronan Synthases; D054990:Idiopathic Pulmonary Fibrosis / Q000473:pathology*; D008168:Lung / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D053773:Transforming Growth Factor beta1; D014453:Glucuronosyltransferase; C101754:HAS2 protein, human; D000076002:Hyaluronan Synthases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
Fibroblasts; idiopathic pulmonary fibrosis; phenotype transformation; phosphatase and tensin homologue deleted on chromosome 10