Rattus norvegicus
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ABSTRACT:
PROVIDER: PRJNA384003 | ENA |
REPOSITORIES: ENA
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Project description:Wound healing is a complex process regulated by various cell types and a plethora of mediators. While interactions between wounded skin and the hair follicles (HFs) could induce HF neogenesis or promote wound healing, it remains unknown whether the wound healing-associated signaling milieu can be manipulated to protect against alopecia, such as chemotherapy-induced alopecia (CIA). Utilizing a well-established neonatal rat model of CIA, we show here that skin wounding protects from alopecia caused by several clinically relevant chemotherapeutic regimens, and that protection is dependent on the time of wounding and hair cycle stage. Gene expression profiling unveiled a significant increase in interleukin-1 beta (IL-1β) mediated signaling by skin wounding. Subsequently, we showed that IL-1β is sufficient and indispensable for mediating the CIA-protective effect. Administration of IL-1β alone to unwounded rats exhibited local CIA protection while IL-1β neutralization abrogated CIA protection by wounding. Mechanistically, IL-1β retarded postnatal HF morphogenesis, making HFs at the wound sites or IL-1β treated areas damage-resistant while the rats developed total alopecia elsewhere. We conclude that wound healing switches the cutaneous cytokine milieu to an IL-1β-dominated state thus retarding HF growth progression and rendering the HFs resistant to chemotherapy agents. In the future, manipulation of HF progression through interfering with the IL-1β signaling milieu may provide therapeutic benefits to a variety of conditions, from prevention of CIA to inhibition of hair growth and treatment of hirsutism. In this experiment, we used the Rat MI-Ready array comprised of over 34,000 transcript probes for gene and alternative splice products in ENSEMBL release 37 to profile gene expression changes during acute wound healing in rat skin. 16,198 Selected rat probes were above threshold in at least one group. 3,239 significant genes were found (FDR < 0.1).
2017-06-29 | GSE98105 | GEO
Project description:The aim of this experiment was measure the influence of age on cutaneous wound healing using human subjects. Increaded age has been associated with delayed wound healing in mouse models and in humans. Gene expression was compared between excisional biopsy wounds from young and old subjects.
2008-04-10 | E-MEXP-1074 | biostudies-arrayexpress
Project description:To determine whether dural fibroblasts (DuF) under IL-1β-mediated wound conditions, release pro-angiogenic factors, and promote angiogenic properties in human endothelial cells (ECs). DuF were stimulated by pro-inflammatory cytokines interleukin (IL)-1β, and transcriptome sequencing was then used to identify the differentially expressed genes in the DuF with/without IL-1β stimulation (DuFCon/DuFIL1b)
2023-02-15 | GSE224999 | GEO
Project description:Pyroptosis is a lytic cell death mode that helps limit the spread of infections and is also linked to pathology in sterile inflammatory diseases and autoimmune diseases. During pyroptosis, inflammasome activation and the engagement of caspase-1 lead to cell death, along with the maturation and secretion of the inflammatory cytokine interleukin 1β (IL-1β). The dominant effect of IL-1β in promoting tissue inflammation has clouded the potential influence of other factors released from pyroptotic cells. Here, using a system where macrophages are induced to undergo pyroptosis without IL-1β/⍺ release (denoted Pyro-1), we uncover unexpected beneficial effects of the Pyro-1 secretome. First, we noted that the Pyro-1 supernatants upregulated gene signatures linked to migration, cellular proliferation, and wound healing. Consistent with this gene signature, Pyro-1 supernatants boosted migration of primary fibroblasts and macrophages, as well as faster wound closure in vitro, and improved tissue repair in vivo. In mechanistic studies, lipidomics and metabolomics of the Pyro-1 supernatants identified the presence of both oxylipins and metabolites, linking them to pro-wound healing effects. Focusing specifically on the oxylipin prostaglandin E2 (PGE2), we find that PGE2 synthesis is induced de novo during pyroptosis, downstream of caspase-1 activation, and COX2 activity; further, PGE2 synthesis occurs late in pyroptosis, with its release dependent on Gasdermin D pores opened during pyroptosis. As for the pyroptotic metabolites, they link to immune cell infiltration into the wounds, and polarization to CD301+ macrophages. Collectively, these data advance the concept that the pyroptotic secretome 1 Mehrotra et al., Page No. possesses oxylipins and metabolites with tissue repair properties that may be harnessed therapeutically.
2024-04-07 | GSE262847 | GEO
Project description:Impaired skin wound healing is a significant global health issue, especially among the elderly. Wound healing is a well-orchestrated process involving the sequential phases of inflammation, proliferation, and tissue remodeling. Although wound healing is a highly dynamic and energy-requiring process, the role of metabolism remains largely unexplored. By combining transcriptomics and metabolomics of human skin biopsy samples, we mapped the core bioenergetic and metabolic changes in normal acute as well as chronic wounds in elderly subjects. We found upregulation of glycolysis, the tricarboxylic acid cycle, glutaminolysis, and β-oxidation in the later stages of acute wound healing and in chronic wounds. To ascertain the role of these metabolic pathways on wound healing, we targeted each pathway in a wound healing assay as well as in a human skin explant model using metabolic inhibitors and stimulants. Enhancement or inhibition of glycolysis and, to a lesser extent, glutaminolysis had a far greater impact on wound healing than similar manipulations of oxidative phosphorylation and fatty acid β-oxidation. These findings increase the understanding of wound metabolism and identify glycolysis and glutaminolysis as potential targets for therapeutic intervention.
2024-07-02 | MTBLS3315 | MetaboLights
Project description:We here addressed the question whether the unique capacity of mesenchymal stromal/stem cells (MSCs) to re-establish tissue homeostasis depends on their potential to sense pathogen associated molecular pattern (PAMP) and, in consequence, mount an adaptive response in the interest of tissue repair. After injection of MSCs which had been primed with the bacterial wall component LPS into murine wounds, an unexpected acceleration of healing occurred, clearly exceeding that of non-primed MSCs. This correlates with a fundamental reprogramming of the transcriptome in LPS treated MSCs as deduced from RNA-seq analysis and its validation. A network of genes mediating the adaptive response through the TLR-4 pathway responsible for neutrophil activation (GCP- 2, ENA-78, IL-1β IL-8) and MSC protection (SOX6) profoundly contributes to enhanced wound healing. In fact, silencing of either TRL-4, or IRAK3, a downstream effector of TRL-4, or SOX6 suppressed wound healing most likely due to suppression of neutrophil extracellular trap formation and suppression of the enhanced microbicidal release of reactive oxygen species (ROS), key features of neutrophil activation. This previously unreported results uncover SOX6 which protects MSCs at the wound site from enhanced oxidative stress. This unprecedented findings hold substantial promise to refine current MSC-based therapies for difficult-to-treat wounds.
2018-05-09 | GSE114189 | GEO
Project description:Diabetic foot ulcer (DFU) is a common complication of diabetes characterized by increased inflammation and a slowed healing process for wounds. Interleukin-37 (IL-37) may act as an alarm to alert the immune system when released by epithelial barrier tissues during trauma or infection, exerting a broad range of protective effects in several diseases. The objective of this study was to examine the regenerative capabilities of IL-37 in improving the healing of diabetic wounds. Using streptozotocin (STZ)-induced diabetic mice, we found that diabetic IL-37Tg mice showed a significantly accelerated healing process. In addition, IL-37 strongly suppressed MAPK signaling pathway by inhibiting phosphorylation of the P38 and ERK. Moreover, IL-37 reduced the expression of Nod-like receptor protein-3 (NLRP3) and mature IL-1β. These results thus indicated that IL-37 inhibition of IL-1β production is mediated by suppressing the initial priming step and by inhibiting the NLRP3 inflammasome activation. Taken together, our findings demonstrated the promising regulatory activity of IL-37 against IL-1β production and indicated that IL-37 has the potential to be effective as a novel therapeutic agent for treatment of wound. Our data indicate a beneficial effect of IL-37 in diabetic wounds, suggesting a therapeutic potential for this cytokine in diabetic ulcer management.
2025-03-05 | GSE282682 | GEO
Project description:Wound healing is one fundamental physiological process which maintains the integrity of skin through a series of well-orchestrated biological and molecular events,effective resolution of inflammation is crucial for wound healing We used microarrays to characterize molecular mechanisms of wound healing with Spink7 KO mice of up-regulated genes during this process.
2025-04-02 | GSE282599 | GEO
Project description:Cold atmospheric plasma jet (CAPJ) is composed of a variety of reactive species and has been demonstrated to have an effect on promoting wound healing. However, not all served-subjects respond equally to CAPJ, and indeed the underlying cellular mechanisms are rarely understood. Proteomics results clearly revealed that wound repair in keratinocytes was accelerated by plasma-activated medium (PAM) treatment through phosphorylating CK2-coordinated PI3K/AKT and MAPK signaling pathways, activating their downstream physiological responses for cell migration, proliferation and extracellular vesicles mediated cell-cell communication. Moreover, CAPJ-treated wound tissues showed a denser and well-organized extracellular matrix (ECM) architecture, implying the speed-up of epithelialization in wound healing. This study unveiled the primary cellular responses affected by CAPJ during wound
repair, providing valuable insights for the treatment selection and the development of therapeutic strategies to achieve better therapy outcomes.
2025-04-17 | PXD051544 | JPOST Repository
Project description:To identify the candidate miRNAs that might compromise wound healing and contribute to the age-associated delay in wound repair, global miRNA profiling was performed in mouse back telogen skin of young (8-week-old) and aged (2-year-old) animals.
2017-03-25 | GSE97034 | GEO