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Pazzaglia, S.* ; Tanno, B.* ; De Stefano, I.* ; Giardullo, P.* ; Leonardi, S.* ; Merla, C.* ; Babini, G.* ; Tuncay Cagatay, S.* ; Mayah, A.* ; Kadhim, M.* ; Lyng, F.M.* ; von Toerne, C. ; Zhan, Z.N. ; Subedi, P. ; Tapio, S. ; Saran, A.* ; Mancuso, M.*

Micro-RNA and proteomic profiles of plasma-derived exosomes from irradiated mice reveal molecular changes preventing apoptosis in neonatal cerebellum.

Int. J. Mol. Sci. 23:2169 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Cell communication via exosomes is capable of influencing cell fate in stress situations such as exposure to ionizing radiation. In vitro and in vivo studies have shown that exosomes might play a role in out-of-target radiation effects by carrying molecular signaling mediators of radiation damage, as well as opposite protective functions resulting in resistance to radiotherapy. However, a global understanding of exosomes and their radiation-induced regulation, especially within the context of an intact mammalian organism, has been lacking. In this in vivo study, we demonstrate that, compared to sham-irradiated (SI) mice, a distinct pattern of proteins and miRNAs is found packaged into circulating plasma exosomes after whole-body and partial-body irradiation (WBI and PBI) with 2 Gy X-rays. A high number of deregulated proteins (59% of WBI and 67% of PBI) was found in the exosomes of irradiated mice. In total, 57 and 13 miRNAs were deregulated in WBI and PBI groups, respectively, suggesting that the miRNA cargo is influenced by the tissue volume exposed to radiation. In addition, five miRNAs (miR-99b-3p, miR-200a-3p, miR-200a, miR-182-5p, miR-182) were commonly overexpressed in the exosomes from the WBI and PBI groups. In this study, particular emphasis was also given to the determination of the in vivo effect of exosome transfer by intracranial injection in the highly radiosensitive neonatal cerebellum at postnatal day 3. In accordance with a major overall anti-apoptotic function of the commonly deregulated miRNAs, here, we report that exosomes from the plasma of irradiated mice, especially in the case of WBI, prevent radiation-induced apoptosis, thus holding promise for exosome-based future therapeutic applications against radiation injury.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Apoptosis ; Exosomes ; Ionizing Radiation ; Mirnome ; Neonatal Cerebellum ; Proteomics; Mesenchymal Stem-cells; Extracellular Vesicles; Ionizing-radiation; Dna-damage; Bystander; Insights; Cancer; Mouse; Proliferation; Instability
ISSN (print) / ISBN 1422-0067
e-ISSN 1661-6596
Zeitschrift International Journal of Molecular Sciences
Quellenangaben Band: 23, Heft: 4, Seiten: , Artikelnummer: 2169 Supplement: ,
Verlag MDPI
Verlagsort Basel
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) CF Metabolomics & Proteomics (CF-MPC)
Institute of Biological and Medical Imaging (IBMI)
Institute of Radiation Medicine (IRM)
Förderungen SEPARATE project from Euratom Research and training programme 2014-2018