{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:51:44Z","timestamp":1787237504664,"version":"build-2736575974"},"reference-count":89,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T00:00:00Z","timestamp":1625011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["02NUK047D"],"award-info":[{"award-number":["02NUK047D"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GRK1739\/2"],"award-info":[{"award-number":["GRK1739\/2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Radiation-induced damage to normal lung parenchyma remains a dose-limiting factor in thorax-associated radiotherapy (RT). Severe early and late complications with lungs can increase the risk of morbidity in cancer patients after RT. Herein, senescence of lung epithelial cells following RT-induced cellular stress, or more precisely the respective altered secretory profile, the senescence-associated secretory phenotype (SASP), was suggested as a central process for the initiation and progression of pneumonitis and pulmonary fibrosis. We previously reported that abrogation of certain aspects of the secretome of senescent lung cells, in particular, signaling inhibition of the SASP-factor Ccl2\/Mcp1 mediated radioprotection especially by limiting endothelial dysfunction. Here, we investigated the therapeutic potential of a combined metformin treatment to protect normal lung tissue from RT-induced senescence and associated lung injury using a preclinical mouse model of radiation-induced pneumopathy. Metformin treatment efficiently limited RT-induced senescence and SASP expression levels, thereby limiting vascular dysfunctions, namely increased vascular permeability associated with increased extravasation of circulating immune and tumor cells early after irradiation (acute effects). Complementary in vitro studies using normal lung epithelial cell lines confirmed the senescence-limiting effect of metformin following RT finally resulting in radioprotection, while fostering RT-induced cellular stress of cultured malignant epithelial cells accounting for radiosensitization. The radioprotective action of metformin for normal lung tissue without simultaneous protection or preferable radiosensitization of tumor tissue might increase tumor control probabilities and survival because higher radiation doses could be used.<\/jats:p>","DOI":"10.3390\/ijms22137064","type":"journal-article","created":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T10:03:19Z","timestamp":1625047399000},"page":"7064","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Metformin Protects against Radiation-Induced Acute Effects by Limiting Senescence of Bronchial-Epithelial Cells"],"prefix":"10.3390","volume":"22","author":[{"given":"Christine","family":"Hansel","sequence":"first","affiliation":[{"name":"Institute of Cell Biology (Cancer Research), University Hospital, Essen, University of Duisburg-Essen, 45122 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3956-3620","authenticated-orcid":false,"given":"Samantha","family":"Barr","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology (Cancer Research), University Hospital, Essen, University of Duisburg-Essen, 45122 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina V.","family":"Schemann","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology (Cancer Research), University Hospital, Essen, University of Duisburg-Essen, 45122 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Lauber","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Hospital, LMU M\u00fcnchen, 80539 Munich, Germany"},{"name":"German Cancer Consortium (DKTK), Partner Site Munich, 80539 Munich, Germany"},{"name":"Clinical Cooperation Group \u2018Personalized Radiotherapy in Head and Neck Cancer\u2019 Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health GmbH, 85764 Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9860-1426","authenticated-orcid":false,"given":"Julia","family":"Hess","sequence":"additional","affiliation":[{"name":"Clinical Cooperation Group \u2018Personalized Radiotherapy in Head and Neck Cancer\u2019 Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health GmbH, 85764 Neuherberg, Germany"},{"name":"Research Unit Radiation Cytogenetics, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health GmbH, 85764 Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian","family":"Unger","sequence":"additional","affiliation":[{"name":"Clinical Cooperation Group \u2018Personalized Radiotherapy in Head and Neck Cancer\u2019 Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health GmbH, 85764 Neuherberg, Germany"},{"name":"Research Unit Radiation Cytogenetics, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health GmbH, 85764 Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horst","family":"Zitzelsberger","sequence":"additional","affiliation":[{"name":"Clinical Cooperation Group \u2018Personalized Radiotherapy in Head and Neck Cancer\u2019 Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health GmbH, 85764 Neuherberg, Germany"},{"name":"Research Unit Radiation Cytogenetics, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health GmbH, 85764 Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1058-2107","authenticated-orcid":false,"given":"Verena","family":"Jendrossek","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology (Cancer Research), University Hospital, Essen, University of Duisburg-Essen, 45122 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1770-443X","authenticated-orcid":false,"given":"Diana","family":"Klein","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology (Cancer Research), University Hospital, Essen, University of Duisburg-Essen, 45122 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s10238-019-00571-w","article-title":"Radiation-induced lung injury: Latest molecular developments, therapeutic approaches, and clinical guidance","volume":"19","author":"Lu","year":"2019","journal-title":"Clin. 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