title: HSPB1 Inhibits the Endothelial-to-Mesenchymal Transition to Suppress Pulmonary Fibrosis and Lung Tumorigenesis.
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.
authors.affiliation: Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Seo-Hyun
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Jae-Kyung
authors.initials: JK
authors.lastname: Nam
authors.affiliation: Division of Constitutional Medicine Research, Korea Institute of Oriental Medicine, Daejeon, Korea.
authors.forename: Bu-Yeo
authors.initials: BY
authors.lastname: Kim
authors.affiliation: Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Junho
authors.initials: J
authors.lastname: Jang
authors.affiliation: Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Young-Bae
authors.initials: YB
authors.lastname: Jin
authors.affiliation: Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Hae-June
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Seungwoo
authors.initials: S
authors.lastname: Park
authors.affiliation: Research Center for Radiotherapy, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Ji
authors.affiliation: Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jaeho
authors.initials: J
authors.lastname: Cho
authors.affiliation: Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul, Korea. yjlee8@kcch.re.kr.
authors.forename: Yoon-Jin
authors.initials: YJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000528:radiation effects; D055551:HSP27 Heat-Shock Proteins / Q000032:analysis / Q000172:deficiency / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000032:analysis / Q000502:physiology*; D006801:Humans; D053612:Janus Kinases / Q000502:physiology; D008175:Lung Neoplasms / Q000209:etiology / Q000517:prevention & control*; D051379:Mice; D008822:Mice, Transgenic; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000032:analysis / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000517:prevention & control*; D050796:STAT3 Transcription Factor / Q000502:physiology
chemical_list: D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D050796:STAT3 Transcription Factor; D053612:Janus Kinases