Exosomes are involved in total body irradiation-induced intestinal injury in mice

Li, Hang; Jiang, Mian; Zhao, Shu-ya; Zhang, Shuqin; Lu, Lu; He, Xin; Feng, Guoxing; Wu, Xin; Fan, Saijun

doi:10.1038/s41401-021-00615-6

Cited by 12 publications

(15 citation statements)

References 67 publications

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“…Most probably, radiation-induced bystander effects mediated by EVs were realized partly by similar mechanisms to direct irradiation, since EVs could induce similar levels of apoptosis in those cell subpopulations, in which direct irradiation also induced apoptosis. This result is consistent with the findings from Li et al, who proved the ability of serum EVs from high-dose-irradiated mice to induce apoptosis in the gastrointestinal tract of EV-recipient mice [ 55 ]. While direct irradiation led to no significant increase in migration of BM stem cells into the spleen, a moderate but significant HSPC migration was demonstrated in mice treated with 0.25Gy EVs.…”

Section: Discussionsupporting

confidence: 93%

Extracellular Vesicles Derived from Bone Marrow in an Early Stage of Ionizing Radiation Damage Are Able to Induce Bystander Responses in the Bone Marrow

Kis

Csordás²,

Persa³

et al. 2022

Cells

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Ionizing radiation (IR)-induced bystander effects contribute to biological responses to radiation, and extracellular vesicles (EVs) play important roles in mediating these effects. In this study we investigated the role of bone marrow (BM)-derived EVs in the bystander transfer of radiation damage. Mice were irradiated with 0.1Gy, 0.25Gy and 2Gy, EVs were extracted from the BM supernatant 24 h or 3 months after irradiation and injected into bystander mice. Acute effects on directly irradiated or EV-treated mice were investigated after 4 and 24 h, while late effects were investigated 3 months after treatment. The acute effects of EVs on the hematopoietic stem and progenitor cell pools were similar to direct irradiation effects and persisted for up to 3 months, with the hematopoietic stem cells showing the strongest bystander responses. EVs isolated 3 months after irradiation elicited no bystander responses. The level of seven microRNAs (miR-33a-3p, miR-140-3p, miR-152-3p, miR-199a-5p, miR-200c-5p, miR-375-3p and miR-669o-5p) was altered in the EVs isolated 24 hour but not 3 months after irradiation. They regulated pathways highly relevant for the cellular response to IR, indicating their role in EV-mediated bystander responses. In conclusion, we showed that only EVs from an early stage of radiation damage could transmit IR-induced bystander effects.

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Section: Discussionsupporting

confidence: 93%

Extracellular Vesicles Derived from Bone Marrow in an Early Stage of Ionizing Radiation Damage Are Able to Induce Bystander Responses in the Bone Marrow

Kis

Csordás²,

Persa³

et al. 2022

Cells

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“…Numerous reports have shown that exosomes not only function in cell-to-cell communication but are also responsible for information delivery during many physiological or pathological processes in vivo. , Our previous research documented different effects of exosomes secreted in mice at various time points following radiation exposure on radiation-mediated GI toxicity . Here, our group first revealed the protective effect of exosomes produced in mice after 6 h of radiation against TBI-induced intestinal injury.…”

Section: Results and Discussionmentioning

confidence: 99%

Biomodified Extracellular Vesicles Remodel the Intestinal Microenvironment to Overcome Radiation Enteritis

Zhao

Jiang

et al. 2023

ACS Nano

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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.

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“…The H&E staining of major organs (Figure S20) after CRT treatment could further prove the safety of as-prepared prodrug NS. Considering the similar significant body weight loss of the RT and CRT groups (Figure E), these aberrant serum chemical indices could be attributed to intestinal injury and the decreased appetite caused by RT, which further caused low protein ingestion …”

Section: Resultsmentioning

confidence: 99%

“…Considering the similar significant body weight loss of the RT and CRT groups (Figure 6E), these aberrant serum chemical indices could be attributed to intestinal injury and the decreased appetite caused by RT, which further caused low protein ingestion. 87…”

Section: In Vivo Anti-tumor Efficacy Of Ngm Micelles Co-administered ...mentioning

confidence: 99%

Prodrug Nanosensitizer Overcomes the Radiation Resistance of Hypoxic Tumor

Qian

Ding

et al. 2022

ACS Appl. Mater. Interfaces

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Clinical radiation therapy (RT) is often hindered by the low radiation energy absorption coefficient and the hypoxic features of tumor tissues. Among the tremendous efforts devoted to overcoming the barriers to efficient RT, the application of hypoxic radiosensitizers and cell-cycle-specific chemotherapeutics has shown great potential. However, their effectiveness is often compromised by their limited bioavailability, especially in the hypoxic region, which plays a major role in radioresistance. Herein, to simultaneously improve the delivery efficacy of both hypoxic radiosensitizer and cell-cycle-specific drug, a gambogic acid (GA) metronidazole (MN) prodrug (GM) was designed and synthesized based on GA, a naturally occurring chemotherapeutic and multiple pathway inhibitor, and MN, a typical hypoxic radiosensitizer. In combination with MN-containing block copolymers, the prodrug nanosensitizer (NS) of GM was obtained. Owing to the bioreduction of MN, the as-designed prodrug could be efficiently delivered to hypoxic cells and act on mitochondria to cause the accumulation of reactive oxygen species. The strong G 2 /M phase arrest caused by the prodrug NS could further sensitize treated cells to external radiation under hypoxic conditions by increasing DNA damage and delaying DNA repair. After coadministration of the NS with a well-established tissue-penetrating peptide, efficient tumor accumulation, deep tumor penetration, and highly potent chemoradiotherapy could be achieved.

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Exosomes are involved in total body irradiation-induced intestinal injury in mice

Cited by 12 publications

References 67 publications

Extracellular Vesicles Derived from Bone Marrow in an Early Stage of Ionizing Radiation Damage Are Able to Induce Bystander Responses in the Bone Marrow

Extracellular Vesicles Derived from Bone Marrow in an Early Stage of Ionizing Radiation Damage Are Able to Induce Bystander Responses in the Bone Marrow

Biomodified Extracellular Vesicles Remodel the Intestinal Microenvironment to Overcome Radiation Enteritis

Prodrug Nanosensitizer Overcomes the Radiation Resistance of Hypoxic Tumor

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