期刊
EXPERIMENTAL CELL RESEARCH
卷 318, 期 15, 页码 1926-1932出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2012.05.023
关键词
Reactive oxygen species; Normal human epidermal keratinocyte; Epithelial to mesenchymal transition; Transforming growth factor-beta 1; Epithelial cadherin; alpha-smooth muscle actin
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [20390475, 23390468]
- Strategic Study Base Formation Support Business [S1001059]
- Grants-in-Aid for Scientific Research [20390475, 23390468] Funding Source: KAKEN
Epithelial to mesenchymal transition (EMT) plays an important role in tumor progression, and is an early step in carcinogenesis. Although reactive oxygen species (ROS) are known to be implicated in EMT in many tumor cell types, its exact role in EMT initiation in normal human cells, especially epidermal keratinocytes (NHEKs), remains unknown. To clarify whether ROS induce EMT in NHEKs, and to establish how ROS regulate EMT, we examined the effect of hydrogen peroxide (H2O2) on the expression of molecules involved in EMT and cell morphology in NHEKs. H2O2 altered the expression of EMT biomarkers, including downregulation of epithelial cadherin and upregulation of alpha-smooth muscle actin, through a transcriptional modulator, Snail1. H2O2 also induced epithelial to fibroblast-like morphological changes, together with upregulation of EMT biomarkers, and promoted phosphorylation of ERK1/2 and JNK in a time-dependent manner. Interestingly, H2O2 stimulated the expression and secretion of TGF-beta 1 in NHEKs. Exogenous TGF-beta 1 also induced the expression of EMT biomarkers. In contrast, neutralizing antibody anti-TGF-beta 1 antibody or inhibitor of TGF-beta receptor type I suppressed the expression of EMT biomarkers. Our results suggest that ROS stimulated TGF-beta 1 secretion and MAPK activation, resulting in EMT initiation in NHEKs. (C) 2012 Elsevier Inc. All rights reserved.
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