Micro-RNA and Proteomic Profiles of Plasma-Derived Exosomes from Irradiated Mice Reveal Molecular Changes Preventing Apoptosis in Neonatal Cerebellum

Abstract

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.

Extracellular vesicle dynamics in COPD: understanding the role of miR-422a, SPP1 and IL-17 A in smoking-related pathology

“…Concerning miR-99b-3p, mesenchymal stem cell-derived EVs (MSC-EVs) promote autophagy of microglial cells through the transfer of miR-99b-3p, thereby relieving neuropathic pain [56]. It may also have an anti-apoptotic/anti-cell death effect in radiation-induced or intraperitoneal disease [57,58]. Regarding miR-422a, plasma exosomal miR-422a serves as the optimal diagnostic biomarker for ischemic stroke [59].…”

MiRNA-Mediated Fibrosis in the Out-of-Target Heart following Partial-Body Irradiation

“…Furthermore, in another recent manuscript [ 51 ], we performed an NGS-based miRNome analysis of plasma exosomes from mice irradiated using the same experimental conditions and with the same radiation doses reported here (SI, PBI and WBI) 24 h post-irradiation. Compared with SI mice, we found 57 significantly differentially expressed miRNAs in plasma exosomes from WBI mice, 13 from PBI mice and only 5 in common between the two different irradiation conditions.…”

Passive Microwave Radiometry and microRNA Detection for Breast Cancer Diagnostics

“…In vitro and in vivo studies have shown that exosomes may play a role in off-target radiation effects by carrying molecular signaling mediators of radiation damage, as well as performing protective functions that lead to resistance to radiation therapy. Moreover, miRNA expression is affected by tissue exposure to radiation, and exosomes from the plasma of irradiated mice prevent radiation-induced apoptosis [19]. Thus, the main factor that transmits information is the quantitative and qualitative miRNA composition of exosomes.…”