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Induction of MiR-21 by Stereotactic Body Radiotherapy Contributes to the Pulmonary Fibrotic Response

Title
Induction of MiR-21 by Stereotactic Body Radiotherapy Contributes to the Pulmonary Fibrotic Response
Authors
Kwon, Ok-SeonKim, Keun-TaeLee, EuniooKim, MyoungjaeChoi, Seo-HyunLi, HenghongFornace, Albert J., Jr.Cho, Jae-HoLee, Yun-SilLee, Ji-SeonLee, Yoon-JinCha, Hyuk-Jin
Ewha Authors
이윤실
SCOPUS Author ID
이윤실scopus
Issue Date
2016
Journal Title
PLOS ONE
ISSN
1932-6203JCR Link
Citation
vol. 11, no. 5
Publisher
PUBLIC LIBRARY SCIENCE
Indexed
SCIE; SCOPUS WOS scopus
Abstract
Radiation-induced lung fibrosis, the most serious effect of lung cancer radiotherapy on normal tissue, remains a major technical obstacle to the broader application of radiotherapy to patients with lung cancer. This study describes the use of an image-guided irradiation system in mice mimicking stereotactic body radiotherapy (SBRT) to examine the molecular features of chronic fibrotic response after radiation injury. MicroRNA (miR) array analysis of injured pulmonary tissue identified a set of miRs whose expression was significantly increased in damaged lung tissue. In particular, miR-21 expression was increased at the radiation injury site, concurrent with collagen deposition. Although the inhibition of miR-21 by its specific inhibitor anti-miR-21 only marginally affected endothelial-mesenchymal transition (EndMT) in lung endothelial cells, this inhibition significantly reduced collagen synthesis in lung fibroblasts. Furthermore, ectopic expression of miR-21 was sufficient to promote a fibrotic response in lung fibroblasts, enhancing Smad2 phosphorylation concurrent with Smad7 downregulation. These findings indicate that the induction of miR-21 expression is responsible for fibrotic responses observed in mesenchymal cells at the injury site through the potentiation of TGF-beta signaling. Local targeting of miR-21 at the injured area could have potential therapeutic utility in mitigating radiation-induced lung fibrosis.
DOI
10.1371/journal.pone.0154942
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약학대학 > 약학과 > Journal papers
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