{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T04:18:07Z","timestamp":1788841087865,"version":"build-2803163510"},"reference-count":82,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,21]],"date-time":"2023-01-21T00:00:00Z","timestamp":1674259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Opportunity Funds Management Core of the Centers for Medical Countermeasures against Radiation","award":["U19AI067773"],"award-info":[{"award-number":["U19AI067773"]}]},{"name":"Opportunity Funds Management Core of the Centers for Medical Countermeasures against Radiation","award":["5U19AI067773-14"],"award-info":[{"award-number":["5U19AI067773-14"]}]},{"name":"Opportunity Funds Management Core of the Centers for Medical Countermeasures against Radiation","award":["DM178018"],"award-info":[{"award-number":["DM178018"]}]},{"name":"National Institutes of Health (NIH)","award":["U19AI067773"],"award-info":[{"award-number":["U19AI067773"]}]},{"name":"National Institutes of Health (NIH)","award":["5U19AI067773-14"],"award-info":[{"award-number":["5U19AI067773-14"]}]},{"name":"National Institutes of Health (NIH)","award":["DM178018"],"award-info":[{"award-number":["DM178018"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19AI067773"],"award-info":[{"award-number":["U19AI067773"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["5U19AI067773-14"],"award-info":[{"award-number":["5U19AI067773-14"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["DM178018"],"award-info":[{"award-number":["DM178018"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009898","name":"Defense Medical Research and Materiel Command","doi-asserted-by":"publisher","award":["U19AI067773"],"award-info":[{"award-number":["U19AI067773"]}],"id":[{"id":"10.13039\/100009898","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009898","name":"Defense Medical Research and Materiel Command","doi-asserted-by":"publisher","award":["5U19AI067773-14"],"award-info":[{"award-number":["5U19AI067773-14"]}],"id":[{"id":"10.13039\/100009898","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009898","name":"Defense Medical Research and Materiel Command","doi-asserted-by":"publisher","award":["DM178018"],"award-info":[{"award-number":["DM178018"]}],"id":[{"id":"10.13039\/100009898","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NASA fellowship to Michelle Bylicky","award":["U19AI067773"],"award-info":[{"award-number":["U19AI067773"]}]},{"name":"NASA fellowship to Michelle Bylicky","award":["5U19AI067773-14"],"award-info":[{"award-number":["5U19AI067773-14"]}]},{"name":"NASA fellowship to Michelle Bylicky","award":["DM178018"],"award-info":[{"award-number":["DM178018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Low dose-rate radiation exposure can occur in medical imaging, as background from environmental or industrial radiation, and is a hazard of space travel. In contrast with high dose-rate radiation exposure that can induce acute life-threatening syndromes, chronic low-dose radiation is associated with Chronic Radiation Syndrome (CRS), which can alter environmental sensitivity. Secondary effects of chronic low dose-rate radiation exposure include circulatory, digestive, cardiovascular, and neurological diseases, as well as cancer. Here, we investigated 1\u20132 Gy, 0.66 cGy\/h, 60Co radiation effects on primary human mesenchymal stem cells (hMSC). There was no significant induction of apoptosis or DNA damage, and cells continued to proliferate. Gene ontology (GO) analysis of transcriptome changes revealed alterations in pathways related to cellular metabolism (cholesterol, fatty acid, and glucose metabolism), extracellular matrix modification and cell adhesion\/migration, and regulation of vasoconstriction and inflammation. Interestingly, there was increased hypoxia signaling and increased activation of pathways regulated by iron deficiency, but Nrf2 and related genes were reduced. The data were validated in hMSC and human lung microvascular endothelial cells using targeted qPCR and Western blotting. Notably absent in the GO analysis were alteration pathways for DNA damage response, cell cycle inhibition, senescence, and pro-inflammatory response that we previously observed for high dose-rate radiation exposure. Our findings suggest that cellular gene transcription response to low dose-rate ionizing radiation is fundamentally different compared to high-dose-rate exposure. We hypothesize that cellular response to hypoxia and iron deficiency are driving processes, upstream of the other pathway regulation.<\/jats:p>","DOI":"10.3390\/antiox12020241","type":"journal-article","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T03:21:54Z","timestamp":1674616914000},"page":"241","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Transcriptomic Profiling and Pathway Analysis of Mesenchymal Stem Cells Following Low Dose-Rate Radiation Exposure"],"prefix":"10.3390","volume":"12","author":[{"given":"John E.","family":"Slaven","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Wilkerson","sequence":"additional","affiliation":[{"name":"Collaborative Health Initiative Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"},{"name":"Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony R.","family":"Soltis","sequence":"additional","affiliation":[{"name":"Collaborative Health Initiative Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"},{"name":"Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Bradley","family":"Rittase","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry T.","family":"Bradfield","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Bylicky","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5548-9489","authenticated-orcid":false,"given":"Lynnette","family":"Cary","sequence":"additional","affiliation":[{"name":"Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena","family":"Tsioplaya","sequence":"additional","affiliation":[{"name":"Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxane","family":"Bouten","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifton","family":"Dalgard","sequence":"additional","affiliation":[{"name":"The American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"},{"name":"Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina M.","family":"Day","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e127","DOI":"10.1002\/mco2.127","article-title":"Redox signaling at the crossroads of human health and disease","volume":"3","author":"Zuo","year":"2022","journal-title":"MedComm"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Tretter, V., Hochreiter, B., Zach, M., Krenn, K., and Klein, K. 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