title: Radiation increases the cellular uptake of exosomes through CD29/CD81 complex formation.
abstract: Exosomes mediate intercellular communication, and mesenchymal stem cells (MSC) or their secreted exosomes affect a number of pathophysiologic states. Clinical applications of MSC and exosomes are increasingly anticipated. Radiation therapy is the main therapeutic tool for a number of various conditions. The cellular uptake mechanisms of exosomes and the effects of radiation on exosome-cell interactions are crucial, but they are not well understood. Here we examined the basic mechanisms and effects of radiation on exosome uptake processes in MSC. Radiation increased the cellular uptake of exosomes. Radiation markedly enhanced the initial cellular attachment to exosomes and induced the colocalization of integrin CD29 and tetraspanin CD81 on the cell surface without affecting their expression levels. Exosomes dominantly bound to the CD29/CD81 complex. Knockdown of CD29 completely inhibited the radiation-induced uptake, and additional or single knockdown of CD81 inhibited basal uptake as well as the increase in radiation-induced uptake. We also examined possible exosome uptake processes affected by radiation. Radiation-induced changes did not involve dynamin2, reactive oxygen species, or their evoked p38 mitogen-activated protein kinase-dependent endocytic or pinocytic pathways. Radiation increased the cellular uptake of exosomes through CD29/CD81 complex formation. These findings provide essential basic insights for potential therapeutic applications of exosomes or MSC in combination with radiation.
authors.affiliation: Research Center for Radiation Emergency Medicine, National Institute of Radiological Science, 4-9-1 Anagawa, Inage, Chiba 263-8555, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Hazawa
authors.affiliation: Research Center for Radiation Emergency Medicine, National Institute of Radiological Science, 4-9-1 Anagawa, Inage, Chiba 263-8555, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Tomiyama
authors.affiliation: Research Center for Radiation Emergency Medicine, National Institute of Radiological Science, 4-9-1 Anagawa, Inage, Chiba 263-8555, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Saotome-Nakamura
authors.affiliation: Research Center for Radiation Emergency Medicine, National Institute of Radiological Science, 4-9-1 Anagawa, Inage, Chiba 263-8555, Japan.
authors.forename: Chizuka
authors.initials: C
authors.lastname: Obara
authors.affiliation: Research Center for Radiation Emergency Medicine, National Institute of Radiological Science, 4-9-1 Anagawa, Inage, Chiba 263-8555, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yasuda
authors.affiliation: Research Center for Radiation Emergency Medicine, National Institute of Radiological Science, 4-9-1 Anagawa, Inage, Chiba 263-8555, Japan.
authors.forename: Takaya
authors.initials: T
authors.lastname: Gotoh
authors.affiliation: Research Center for Radiation Emergency Medicine, National Institute of Radiological Science, 4-9-1 Anagawa, Inage, Chiba 263-8555, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Tanaka
authors.affiliation: Research Center for Radiation Emergency Medicine, National Institute of Radiological Science, 4-9-1 Anagawa, Inage, Chiba 263-8555, Japan.
authors.forename: Haruko
authors.initials: H
authors.lastname: Yakumaru
authors.affiliation: Research Center for Radiation Emergency Medicine, National Institute of Radiological Science, 4-9-1 Anagawa, Inage, Chiba 263-8555, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishihara
authors.affiliation: Research Center for Radiation Emergency Medicine, National Institute of Radiological Science, 4-9-1 Anagawa, Inage, Chiba 263-8555, Japan. Electronic address: tajima@nirs.go.jp.
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tajima
mesh_terms: D002460:Cell Line; D034285:Dynamin II / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism / Q000528:radiation effects*; D005720:Gamma Rays; D055785:Gene Knockdown Techniques; D006801:Humans; D039001:Integrin alpha Chains / Q000378:metabolism; D019012:Integrin beta1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D018384:Oxidative Stress; D060225:Tetraspanin 28 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: D039001:Integrin alpha Chains; D019012:Integrin beta1; D060225:Tetraspanin 28; D034285:Dynamin II
keywords: Dynamin; Integrin; Mesenchymal stem cell; Radiation; Tetraspanin