Persistent mRNA and miRNA expression changes in irradiated baboons

Port, Matthias; Hérodin, Françis; Valente, Marco; Drouet, M.; Ostheim, Patrick; Majewski, Matthäus; Abend, Michael

doi:10.1038/s41598-018-33544-2

Cited by 11 publications

(18 citation statements)

References 30 publications

(35 reference statements)

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“…The results from phase II were compared to whole-genome screening results from our earlier conducted male baboon study [19] (S2 Table ). Altogether 32 candidate genes from the baboon screening data (Microarray) were compared to rhesus macaques data (NGS).…”

Section: Phase Iii: Inter-species Validationmentioning

confidence: 99%

“…Altogether 32 candidate genes from the baboon screening data (Microarray) were compared to rhesus macaques data (NGS). Vice versa, nine candidate genes, that were positively validated in rhesus macaques (NGS) from the current study were examined in an already generated baboon whole genome (microarray) screening data file [19]. Only male individuals were included, as the baboon study did not involve females.…”

Section: Phase Iii: Inter-species Validationmentioning

confidence: 99%

“…The nine successfully validated candidate genes (Table 2) from male rhesus macaques were compared to the whole genome microarray screening database from an earlier performed baboon study in males [19]. Vice versa, the 32 validated candidate genes from male baboons were compared to the NGS screening results of the current study on rhesus macaques.…”

Section: Phase Iii: Inter-species Validationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…In irradiated healthy individuals so far little is known about long-term changes in the transcriptome/post-transcriptome [17][18][19]. Recently, we identified persistent gene expression changes in the peripheral blood of sub-lethally irradiated baboons up to about three months after exposure and discussed their impact on long-term health effects [19]. A persistent alteration of the immune response 30 days after high dose partial body irradiation was postulated by another group [18], but overall, the molecular mechanisms and the entanglement with known long-term effects are not well characterized [1].…”

Section: Introductionmentioning

confidence: 99%

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Gene expression changes in male and female rhesus macaque 60 days after irradiation

et al. 2021

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Purpose Transcriptome changes can be expected in survivors after lethal irradiation. We aimed to characterize these in males and females and after different cytokine treatments 60 days after irradiation. Material and methods Male and female rhesus macaques (n = 142) received a whole-body exposure with 700 cGy, from which 60 animals survived. Peripheral whole blood was drawn pre-exposure and before sacrificing the surviving animals after 60 days. Results We evaluated gene expression in a three-phase study design. Phase I was a whole-genome screening (NGS) for mRNAs using five pre- and post-exposure RNA samples from both sexes (n = 20). Differential gene expression (DGE) was calculated between samples of survivors and pre-exposure samples (reference), separately for males and females. 1,243 up- and down-regulated genes were identified with 30–50% more deregulated genes in females. 37 candidate mRNAs were chosen for qRT-PCR validation in phase II using the remaining samples (n = 117). Altogether 17 genes showed (borderline) significant (t-test) DGE in groups of untreated or treated animals. Nine genes (CD248, EDAR, FAM19A5, GAL3ST4, GCNT4, HBG2/1, LRRN1, NOG, SYT14) remained with significant changes and were detected in at least 50% of samples per group. Panther analysis revealed an overlap between both sexes, related to the WNT signaling pathway, cell adhesion and immunological functions. For phase III, we validated the nine genes with candidate genes (n = 32) from an earlier conducted study on male baboons. Altogether 14 out of 41 genes showed a concordantly DGE across both species in a bilateral comparison. Conclusions Sixty days after radiation exposure, we identified (1) sex and cytokine treatment independent transcriptional changes, (2) females with almost twice as much deregulated genes appeared more radio-responsive than males, (3) Panther analysis revealed an association with immunological processes and WNT pathway for both sexes.

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Section: Phase Iii: Inter-species Validationmentioning

confidence: 99%

Section: Phase Iii: Inter-species Validationmentioning

confidence: 99%

Section: Phase Iii: Inter-species Validationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Gene expression changes in male and female rhesus macaque 60 days after irradiation

et al. 2021

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The miR‐126‐5p and miR‐212‐3p in the extracellular vesicles activate monocytes in the early stage of radiation‐induced vascular inflammation implicated in atherosclerosis

Choi

Kim

Lee

et al. 2023

J of Extracellular Vesicle

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People exposed to radiation in cancer therapy and nuclear accidents are at increased risk of cardiovascular outcomes in long-term survivors. Extracellular vesicles (EVs) are involved in radiation-induced endothelial dysfunction, but their role in the early stage of vascular inflammation after radiation exposure remains to be fully understood. Herein, we demonstrate that endothelial cell-derived EVs containing miRNAs initiate monocyte activation in radiation-induced vascular inflammation. In vitro coculture and in vivo experimental data showed that endothelial EVs can be sensitively increased by radiation exposure in a dose-dependent manner, and stimulate monocytes releasing monocytic EVs and adhesion to endothelial cells together with an increase in the expression of genes encoding specific ligands for cell-cell interaction. Small RNA sequencing and transfection using mimics and inhibitors explained that miR-126-5p and miR-212-3p enriched in endothelial EVs initiate vascular inflammation by monocyte activation after radiation exposure. Moreover, miR-126-5p could be detected in the circulating endothelial EVs of radiation-induced atherosclerosis model mice, which was found to be tightly correlated with the atherogenic index of plasma. In summary, our study showed that miR-126-5p and miR-212-3p present in the endothelial EVs mediate the inflammatory signals to activate monocytes in radiation-induced vascular injury. A better understanding of the circulating endothelial EVs content can promote their use as diagnostic and prognostic biomarkers for atherosclerosis after radiation exposure.

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MicroRNA: a novel implication for damage and protection against ionizing radiation

Chen

Cui

Gong

et al. 2021

Environ Sci Pollut Res

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Ionizing radiation (IR) is a form of high energy. It poses a serious threat to organisms, but radiotherapy is a key therapeutic strategy for various cancers. It is significant to reduce radiation injury but maximize the effect of radiotherapy. MicroRNAs (miRNAs) are posttranscriptionally regulatory factors involved in cellular radioresponse. In this review, we show how miRNAs regulate important genes on cellular response to IR-induced damage and how miRNAs participate in IR-induced carcinogenesis. Additionally, we summarize the experimental and clinical evidence for miRNA involvement in radiotherapy and discuss their potential for improvement of radiotherapy. Finally, we highlight the role that miRNAs play in accident exposure to IR or radiotherapy as predictive biomarker. miRNA therapeutics have shown great perspective in radiobiology; miRNA may become a novel strategy for damage and protection against IR.

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Persistent mRNA and miRNA expression changes in irradiated baboons

Cited by 11 publications

References 30 publications

Gene expression changes in male and female rhesus macaque 60 days after irradiation

Gene expression changes in male and female rhesus macaque 60 days after irradiation

The miR‐126‐5p and miR‐212‐3p in the extracellular vesicles activate monocytes in the early stage of radiation‐induced vascular inflammation implicated in atherosclerosis

MicroRNA: a novel implication for damage and protection against ionizing radiation

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