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Abstract

The endothelial-to-mesenchymal transition (EndMT) contributes to cancer, fibrosis, and other pathologic processes. However, the underlying mechanisms are poorly understood. Endothelial HSP1 (HSPB1) protects against cellular stress and has been implicated in cancer progression and pulmonary fibrosis. In this study, we investigated the role of HSPB1 in mediating the EndMT during the development of pulmonary fibrosis and lung cancer. HSPB1 silencing in human pulmonary endothelial cells accelerated emergence of the fibrotic phenotype after treatment with TGFβ or other cytokines linked to pulmonary fibrosis, suggesting that HSPB1 maintains endothelial cell identity. In mice, endothelial-specific overexpression of HSPB1 was sufficient to inhibit pulmonary fibrosis by blocking the EndMT. Conversely, HSPB1 depletion in a mouse model of lung tumorigenesis induced the EndMT. In clinical specimens of non-small cell lung cancer, HSPB1 expression was absent from tumor endothelial cells undergoing the EndMT. Our results showed that HSPB1 regulated the EndMT in lung fibrosis and cancer, suggesting that HSPB1-targeted therapeutic strategies may be applicable for treating an array of fibrotic diseases.  

Author information

Choi SH1, Nam JK1, Kim BY2, Jang J1, Jin YB1, Lee HJ1, Park S3, Ji YH3, Cho J4, Lee YJ5.

1Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.

2Division of Constitutional Medicine Research, Korea Institute of Oriental Medicine, Daejeon, Korea.

3Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.

4Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Korea.

5Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul, Korea. yjlee8@kcch.re.kr.