Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, P.R. China.
Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province China.
ACS Nano. 2023 Jul 25;17(14):14079-14098. doi: 10.1021/acsnano.3c04578. Epub 2023 Jul 3.
Ionizing radiation (IR) is associated with the occurrence of enteritis, and protecting the whole intestine from radiation-induced gut injury remains an unmet clinical need. Circulating extracellular vesicles (EVs) are proven to be vital factors in the establishment of tissue and cell microenvironments. In this study, we aimed to investigate a radioprotective strategy mediated by small EVs (exosomes) in the context of irradiation-induced intestinal injury. We found that exosomes derived from donor mice exposed to total body irradiation (TBI) could protect recipient mice against TBI-induced lethality and alleviate radiation-induced gastrointestinal (GI) tract toxicity. To enhance the protective effect of EVs, profilings of mouse and human exosomal microRNAs (miRNAs) were performed to identify the functional molecule in exosomes. We found that miRNA-142-5p was highly expressed in exosomes from both donor mice exposed to TBI and patients after radiotherapy (RT). Moreover, miR-142 protected intestinal epithelial cells from irradiation-induced apoptosis and death and mediated EV protection against radiation enteritis by ameliorating the intestinal microenvironment. Then, biomodification of EVs was accomplished via enhancing miR-142 expression and intestinal specificity of exosomes, and thus improved EV-mediated protection from radiation enteritis. Our findings provide an effective approach for protecting against GI syndrome in people exposed to irradiation.
电离辐射（IR）与肠炎的发生有关，保护整个肠道免受辐射引起的肠道损伤仍然是未满足的临床需求。循环细胞外囊泡（EVs）已被证明是建立组织和细胞微环境的重要因素。在这项研究中，我们旨在研究辐射诱导的肠道损伤背景下，由小 EV（外泌体）介导的放射防护策略。我们发现，来自全身照射（TBI）暴露的供体小鼠的外泌体可以保护受体小鼠免受 TBI 诱导的致死作用，并减轻辐射引起的胃肠道（GI）毒性。为了增强 EV 的保护作用，对小鼠和人外泌体 microRNAs（miRNAs）进行了分析，以鉴定外泌体中的功能分子。我们发现，miR-142-5p 在 TBI 暴露的供体小鼠和放射治疗（RT）后的患者来源的外泌体中高表达。此外，miR-142 可保护肠上皮细胞免受照射诱导的凋亡和死亡，并通过改善肠道微环境介导 EV 对辐射性肠炎的保护作用。然后，通过增强 miR-142 的表达和外泌体的肠道特异性，对 EV 进行生物修饰，从而提高 EV 对辐射性肠炎的保护作用。我们的研究结果为保护暴露于照射的人群中的 GI 综合征提供了一种有效的方法。
