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IGFBP7 contributes to epithelial‐mesenchymal transition of HPAEpiC cells in response to radiation
Author(s) -
Zhong Yazhen,
Lin Zechen,
Lin Xianlei,
Lu Jinhua,
Wang Nan,
Huang Siyu,
Wang Yuanyuan,
Zhu Yuan,
Shen Yiwei,
Jiang Jing,
Lin Shengyou
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.28516
Subject(s) - epithelial–mesenchymal transition , mapk/erk pathway , transforming growth factor , vimentin , signal transduction , microbiology and biotechnology , cancer research , mesenchymal stem cell , chemistry , biology , immunology , downregulation and upregulation , biochemistry , immunohistochemistry , gene
Radiation‐induced lung injury (RILI) frequently occurs in patients with thoracic malignancies. In response to radiation, alveolar epithelial cells (AEC) undergo epithelial‐mesenchymal transition (EMT) and contribute to the pathogenesis of RILI. Insulin‐like growth factor binding protein 7 (IGFBP7) is reported as a downstream mediator of transforming growth factor‐β1 (TGF‐β1) pathway, which plays a crucial role in radiation‐induced EMT. In the present study, the levels of IGFBP7 and TGF‐β1 were simultaneously increased in experimental RILI models and radiation‐treated AEC (human pulmonary alveolar epithelial cells [HPAEpic]). The expression of IGFBP7 in radiation‐treated HPAEpic cells was obviously inhibited by the specific inhibitor of TGF‐β receptor antagonist SB431542 and TGF‐β1 neutralizing antibody, and time‐dependently enhanced by TGF‐β1 treatment. Moreover, IGFBP7 knockdown significantly attenuated the effects of radiation on morphology change, cell migration, expression of EMT‐related markers (E‐cadherin, α‐SMA, and Vimentin), and phosphorylation of extracellular‐signal‐regulated kinase (ERK). The effects of IGFBP7 overexpression on the expression of EMT‐related markers were partially reversed by the ERK inhibitor PD98059. In conclusion, IGFBP7, was enhanced by TGF‐β1, may be involved in radiation‐induced EMT of AEC via the ERK signaling pathway, thus contributing to the pathogenesis of RILI.