Phosphatase and tensin homolog deleted on chromosome 10 contributes to phenotype transformation of fibroblasts in idiopathic pulmonary fibrosis via multiple pathways
Phosphatase and tensin homolog deleted on chromosome 10 contributes to phenotype transformation of fibroblasts in idiopathic pulmonary fibrosis via multiple pathways
复制标题
10号染色体上磷酸酶和张力蛋白同源物缺失通过多种途径促进特发性肺纤维化成纤维细胞表型转化
DOI：
10.1177/1535370215600100
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发表时间：
2016-01-01
影响因子：
3.2
通讯作者：
Dai, Huaping
中科院分区：
文献类型：
--
作者：
Geng, Jing;Huang, Xiaoxi;Dai, Huaping
特发性肺纤维化(IPF)是一种进行性和致命性疾病，被认为是一种癌症样疾病。10号染色体上缺失的磷酸酶和张力蛋白同源物(PTEN)肿瘤抑制因子在特发性肺纤维化的发病机制中引起了人们的关注。然而，PTEN在肺成纤维细胞表型转化中的作用，特别是在迁移和侵袭性表型中的作用，仍然是未知的。我们的数据显示，PTEN在IPF患者的成纤维细胞和肌成纤维细胞中的表达均显著降低。此外，PTEN的缺失导致正常成纤维细胞向肌成纤维细胞转化，并增加了增殖、抗凋亡和迁移/侵袭活性。PTEN缺乏上调透明质酸合成酶2的表达，从而增强成纤维细胞的侵袭能力。观察PTEN与转化生长因子-β1(TGF-β1)信号通路的相互作用，以及低氧对PTEN的抑制作用。这些发现表明，PTEN参与了多种途径，在IPF的发病机制中起着关键作用。
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 beta 1 (TGF-beta 1) 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.