Plasma-derived exosomes boost the healing of irradiated wound by regulating cell proliferation and ferroptosis
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ABSTRACT:
PROVIDER: PRJNA682748 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13202238.fastq.gz | Fastqsanger.gz | |||
| SRR13202239.fastq.gz | Fastqsanger.gz | |||
| SRR13202240.fastq.gz | Fastqsanger.gz | |||
| SRR13202241.fastq.gz | Fastqsanger.gz | |||
| SRR13202242.fastq.gz | Fastqsanger.gz |
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Project description:Ionizing radiation (IR) therapy for malignant tumors can damage adjacent tissues, leading to severe wound complications. Plasma-derived exosome treatment has recently emerged as a safe and impactful cell-free therapy. Herein, we aimed to determine whether plasma-derived exosomes could improve the healing of post-radiation wound. Rat plasma-derived exosomes (RP-Exos) were locally injected on cutaneous wounds created on the backs of irradiated rats and boosted the healing process as well as the deposition and remodeling of the extracellular matrix with collagen formation. Subsequently, the effects of RP-Exos were further evaluated on irradiated fibroblasts in vitro. The results suggested that exosomes promoted fibroblast proliferation, migration, cell cycle progression, and cell survival. Moreover, transcriptome sequencing, analysis, and quantitative polymerase chain reaction validation were performed to identify the underlying molecular mechanisms. RP-Exos enhanced the expression of cell proliferation and radioresistance-related genes, and yet downregulated ferroptosis pathway in irradiated fibroblasts. Inhibition of ferroptosis by RP-Exos was further confirmed through colorimetric assay, fluorescence probe and flow cytometry in ferroptosis-induced fibroblasts. Our results suggest that RP-Exos regulate cell proliferation and ferroptosis in radiated fibroblasts, thereby boosting the healing of radiated wounds. These findings support plasma-derived exosomes as a potential therapeutic method for post-radiation wound complications.
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Project description:Mesenchymal stem cell (MSC)-derived exosomes had been reported to be a prospective candidate in accelerating diabetic wound healing. Hence, this study intended to explore whether exosomes originating from the human umbilical cord MSC (hucMSC) could display a superior proangiogenic effect on diabetic wound repair and its underlying molecular mechanism.
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Project description:Extracellular vesicles (EVs) are on the edge of innovation aimed at regenerative and therapeutic applications, including wound healing, by containing therapeutic agents originating from secreting cells. Moreover, silver nanoparticles (AgNPs) play a role in wound healing because they have antiseptic activities. Therefore, in this study, we used sequencing technology to investigate the mRNA profile in UCMSC-derived exosomes (EXs). We also attempted to determine the role of the transcriptome, particularly in cutaneous wound healing, using bioinformatics analysis. Additionally, we investigated the efficacy of utilising a combination of UCMSC-derived EXs and AgNPs on burned animal models. Results showed that a large number of protein-coding genes (4578 genes) have been detected in UCMSC-derived EXs, among which 2004 genes are upregulated in exosomes while 2574 genes are downregulated compared to secreting cells. Interestingly, many genes enriched in exosomes were associated with the biology of the wound healing process. Gene ontology (GO) term and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis indicated the upregulated exosomal genes belonging to GO terms and KEGG pathways related to signaling pathways such as DNA replication, ribosome, cell cycle, and pyrimidine metabolism. Further investigations that aimed to test exosomes and AgNPs in wound healing stimulation confirmed the faster healing capacity belongs to all exosomes, AgNPs, and a combination of EXs and AgNPs in the early healing process. The exosomes also expressed their capacity to enhance the dermal fibroblast proliferation. Our findings indicated the selective sorting of mRNAs into EXs, the potential of EXs, and the combination of EXs with AgNPs in cutaneous wound healing. Extracellular vesicles (EVs) are on the edge of innovation aimed at regenerative and therapeutic applications, including wound healing, by containing therapeutic agents originating from secreting cells. Moreover, silver nanoparticles (AgNPs) play a role in wound healing because they have antiseptic activities. Therefore, in this study, we used sequencing technology to investigate the mRNA profile in UCMSC-derived exosomes (EXs). We also attempted to determine the role of the transcriptome, particularly in cutaneous wound healing, using bioinformatics analysis. Additionally, we investigated the efficacy of utilising a combination of UCMSC-derived EXs and AgNPs on burned animal models. Results showed that a large number of protein-coding genes (4578 genes) have been detected in UCMSC-derived EXs, among which 2004 genes are upregulated in exosomes while 2574 genes are downregulated compared to secreting cells. 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Project description:Terahertz (THz) technology has emerged for biomedical applications such as scanning, molecular spectroscopy, and medical imaging. However, the biological effect of THz radiation is not fully understood. Non-thermal effects of THz radiation were investigated by applying a femtosecond-terahertz (fs-THz) pulse to mouse skin. Analysis of the genome-wide expression profile in fs-THz-irradiated skin indicated that wound responses were predominantly through NF?B1- and Smad3/4-mediated transcriptional activation. Repeated fs-THz radiation delayed the closure of mouse skin punch wounds due to up-regulation of transforming growth factor-beta (TGF-?). These findings suggest that fs-THz radiation provokes a wound-like signal in skin with increased expression of TGF-? and activation of its downstream target genes, which perturbs the wound healing process in vivo. To identify non-thermally induced in vivo mode action of THz radiation, gene expression profile of fs-THz-irradiated skin (at post 24-hours after 1 hour exposure) was explored. Purified total RNAs from independent 3 mice of each sham and THz group were labeled and hybridized on the Mouse Gene 1.0 ST Array (Affymetrix, Santa Clara, CA), according to manufacturer's standard protocol. Statistically filtered THz-responsive genes were examined for possible interactions with other molecules, canonical signaling pathways, and bio-functions.
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