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Integrative small and long RNA-omics analysis of human healing and non-healing wounds discovers cooperating microRNAs as therapeutic targets

ABSTRACT: Integrative small and long RNA-omics analysis of human healing and non-healing wounds discovers cooperating microRNAs as therapeutic targets

PROVIDER: PRJNA807289 | ENA |

REPOSITORIES: ENA

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Integrative small and long RNA-omics analysis of human healing and non-healing wounds discovers cooperating microRNAs as therapeutic targets

Project description:Integrative small and long RNA-omics analysis of human healing and non-healing wounds discovers cooperating microRNAs as therapeutic targets

| PRJNA730912 | ENA

Integrative small and long RNA-omics analysis of human healing and non-healing wounds discovers cooperating microRNAs as therapeutic targets

Project description:Due to microRNAs' (miRs) important functions and high potential for disease diagnosis and therapy, increasing efforts have been put to understand their role in wound repair and identify targetable miRs for wound treatment. However, lack of knowledge about miR-mediated gene expression in human wound tissues hinders the recognition of clinically relevant miRs. Here we profiled genome-wide miR and mRNA expression by RNA-sequencing in the same set of samples from human normal acute wounds and chronic non-healing venous ulcers (VU). By integrative analysis of miR and mRNA omics, we unraveled miR-mediated gene regulatory networks specifically associated with different phases of wound repair or VU. We also identified transcriptional factors and miR arm switching events underpinning the dynamically changed miR expression. In this study, we focused on not only a few top changed miRs, but also the miRs with their targetome enriched in the VU gene signature, such as miR-34a-5p, miR-34c-5p, miR-218-5p, miR-7704, miR-424-5p, miR-450-5p, miR-517b-3p, miR-96-5p, and miR-516b-5p. We confirmed these miRs' targetome in human keratinocytes and fibroblasts using microarrays and demonstrated their functional relevance to VU pathology.

2022-03-06 | GSE174661 | GEO

Circular RNA signatures of human healing and non-healing wounds

Project description:Circular RNA signatures of human healing and non-healing wounds

| PRJNA780818 | ENA

Integrative small and long RNA-omics analysis of human healing and non-healing wounds discovers cooperating microRNAs as therapeutic targets

Project description:We identified pathologically relevant miRs that exhibited abnormal VU expression and displayed their targets enriched explicitly in the VU gene signature. The biological function of these miRNAs in human epidermal keratinocytes or fibroblasts during wound repair remains unclear. To study the genes regulated by miR-96-5p, miR-218-5p, miR-424-5p, miR-450b-5p, miR-516b-5p or miR-7704, we transfected miRNA mimics into human primary epidermal keratinocytes or fibroblasts to overexpress respective miRNA expression. We performed a global transcriptome analysis of keratinocytes or fibroblasts upon miRNA overexpression using Affymetrix arrays.

2022-02-16 | GSE196773 | GEO

Smad7-based biologic targeting epidermis and stroma promotes healing of diabetic wounds in mice and pigs

Project description:Impaired healing of diabetic wounds causes significant morbidity and mortality. This study aimed to identify novel mechanisms of diabetic wound healing defects and test a therapeutic intervention using diabetic mouse and pig models. We found Smad7 transgene expression in mouse epidermis promoting wound healing in diabetic db/db mice, with reductions in obesity and blood glucose. To isolate effects of Smad7 on wounds, we created a Smad7-based biologic (Tat-PYC-Smad7) that penetrates wound cells. Topical application of Tat-PYC-Smad7 to diabetic pig and mouse wounds accelerated healing compared to controls. RNAseq analysis of mouse wound samples showed reduced TGFβ/NFκB signaling, leading to faster re-epithelialization and better extracellular matrix remodeling. Tat-PYC-Smad7 also attenuated neutrophil degranulation and NETosis by blocking histone 3 citrullination and inhibiting myeloperoxidase activities. Our study reveals that Tat-PYC-Smad7 promotes diabetic wound healing by targeting keratinocytes and neutrophils, providing insight into cellular mechanisms of diabetic wound healing defects targetable by Smad7-based therapy.

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Transcription profiling by array of excisional biopsy wounds from young and old human subjects to measure the influence of age on cutaneous wound healing

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

Topical, immunomodulatory epoxy-tiglianes induce biofilm disruption and healing in acute and chronic skin wounds [HEKa]

Project description:The management of antibiotic-resistant, bacterial biofilm infections in chronic skin wounds is a significant clinical challenge. Despite advances in diagnosis, many patients do not derive benefit from current anti-infective/antibiotic therapies. Here we report a novel class of epoxy-tiglianes and demonstrate their antimicrobial activity (modifying bacterial growth and inducing biofilm disruption), with structure/activity relationships established against important human pathogens. In vitro, the lead candidate, EBC-1013 stimulated PKC-dependent neutrophil ROS induction and NETosis, and increased expression of wound healing associated cytokines, chemokines and antimicrobial peptides in keratinocytes and fibroblasts. In vivo, topical EBC-1013 induced rapid resolution of infection with increased matrix remodelling in acute thermal injuries. In chronically-infected, diabetic wounds, treatment induced cytokine/chemokine production, inflammatory cell recruitment and complete healing (in 6/7 wounds) with ordered keratinocyte differentiation. These results highlight a non-antibiotic approach involving contrasting, orthogonal mechanisms of action: targeted biofilm disruption and innate immune induction in the treatment of chronic wounds.

2022-05-12 | GSE202794 | GEO

Topical, immunomodulatory epoxy-tiglianes induce biofilm disruption and healing in acute and chronic skin wounds [HDFa]

2022-05-14 | GSE202952 | GEO

Transcription profiling of wounds from ovariectomized MIF null mice and controls to investigate the role of MIF during wound healing using BALB/C MIF null mice

Project description:The aim of this experiment was to investigate the role of MIF during wound healing using BALB/C MIF null mice and in the context of reduced estrogen-associated impaired healing using ovariectomized mice (a mouse model of age-associated delayed healing). Ageing is associated with delayed cutaneous wound healing resulting from reduced estrogen levels. Macrophage migration inhibitory factor (MIF - NCBI RefSeq: NM_010798) is thought to mediate the effects of estrogen on wound healing. Gene expression was compared between wounds from ovariectomized MIF null mice and controls.

2005-11-05 | E-MEXP-209 | biostudies-arrayexpress

Newly defined ABCB5+ dermal mesenchymal stem cells promote healing of chronic iron overload wounds via secretion of interleukin-1 receptor antagonist

Project description:Here we report the beneficial effects of a newly identified dermal cell subpopulation expressing the ATP-binding cassette subfamily B member 5 (ABCB5) for the therapy of non-healing wounds. Local administration of dermal ABCB5+-derived MSCs attenuated macrophage-dominated inflammation and thereby accelerated healing of full-thickness excisional wounds in the iron overload mouse model mimicking the non-healing state of human venous leg ulcers. The observed beneficial effects were due to interleukin-1 receptor antagonist (IL-1RA) secreted by ABCB5+-derived MSCs, which dampened inflammation and shifted the prevalence of unrestrained pro-inflammatory M1 macrophages towards repair promoting anti-inflammatory M2 macrophages at the wound site. The beneficial anti-inflammatory effect of IL-1RA released from ABCB5+-derived MSCs on human wound macrophages was conserved in humanized NOD-scid IL2rγnull mice. In conclusion, human dermal ABCB5+ cells represent a novel, easy accessible and marker-enriched source of MSCs which holds substantial promise to successfully treat chronic non-healing wounds in humans.

2019-01-30 | GSE125829 | GEO

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