Transcriptomic Profiling of Diabetic Porcine Wound Healing Model Identifies Key Metabolic, Inflammatory, and Oxidative Stress Pathways
Ontology highlight
ABSTRACT:
ORGANISM(S): Sus scrofa
PROVIDER: GSE315429 | GEO | 2026/07/03
REPOSITORIES: GEO
Similar Datasets
Project description:Diabetic foot ulcers (DFUs) are a debilitating diabetes complication in which mitochondrial dysfunction and oxidative stress are prominent but mechanistically unresolved features. Here, we identify the mitochondria-encoded circular RNA circMT-RNR2 as a novel modulator of mitochondrial redox homeostasis in human skin wound healing. CircMT-RNR2 is reduced in DFU patient tissue and diabetic mouse wounds, enriched in dermal fibroblasts, and localized to mitochondria. Its loss impairs fibroblast proliferation, migration, extracellular matrix production, and contraction by destabilizing the mitochondrial antioxidant protein PRDX3, leading to elevated oxidative stress, mitochondrial damage, and mitophagy. In murine and human ex vivo wound models, circMT-RNR2 knockdown delays healing, whereas overexpression accelerates repair and boosts antioxidant defenses. These findings position circMT-RNR2 as a mitochondrial guardian of skin healing and a promising therapeutic target for DFUs.
2026-06-08 | PXD067605 | Pride
Project description:Hsa_circ_0084443 expression level is down-regulated during normal skin wound healing and higher level of hsa_circ_0084443 was found in chronic non-healing diabetic foot ulcers compared to normal wounds. However, the biological function of hsa_circ_0084443 in epidermal keratinocytes during wound repair has not been studied. To study the genes regulated by hsa_circ_0084443, we transfected siRNA targeting hsa_circ_0084443 diagnostic junction into human primary epidermal keratinocytes to knockdown hsa_circ_0084443 expression. We performed a global transcriptome analysis of keratinocytes upon knockdown of hsa_circ_0084443 using Affymetrix arrays.
2019-10-01 | GSE114236 | GEO
Project description:Wound healing is a multi-step process to rapidly restore barrier function. This process is often impaired in diabetic patients resulting in chronic wounds and amputation. We previously found that paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway via topical administration of the BRAF inhibitor vemurafenib accelerates wound healing by activating keratinocyte proliferation and reepithelialization pathways in healthy mice. Herein, we investigated whether this wound healing acceleration also occurs in impaired diabetic wounds and found that topical vemurafenib not only improves wound healing in a murine diabetic wound model, but unexpectedly promotes hair follicle regeneration. Neogenic hair follicles expressing Sox-9, CD34 and K15 were found in wounds of diabetic and non-diabetic mice, and their formation can be prevented by blocking downstream MEK signaling. Thus, topically applied BRAF inhibitors may accelerate wound healing, and promote the restoration of improved skin architecture in both normal and impaired wounds.
2021-05-22 | GSE148037 | GEO
Project description:This a model from the article:
Modeling the effects of treating diabetic wounds with engineered skin
substitutes.
Waugh HV, Sherratt JA. Wound Repair Regen
2007 Jul-Aug;15(4):556-65 17650100
,
Abstract:
In this paper, a novel mathematical model of wound healing in both normal and
diabetic cases is presented, focusing upon the effects of adding two currently
available commercial engineered skin substitute therapies to the wound
(Apligraf) and Dermagraft). Our work extends a previously developed model, which
considers inflammatory and repair macrophage dynamics in normal and diabetic
wound healing. Here, we extend the model to include equations for
platelet-derived growth factor concentration, fibroblast density, collagen
density, and hyaluronan concentration. This enables us to examine the variation
of these components in both normal and diabetic wound healing cases, and to
model the treatment protocols of these therapies. Within the context of our
model, we find that the key component to successful healing in diabetic wounds
is hyaluronan and that the therapies work by increasing the amount of hyaluronan
available in the wound environment. The time-to-healing results correlate with
those observed in clinical trials and the model goes some way to establishing an
understanding of why diabetic wounds do not heal, and how these treatments
affect the diabetic wound environment to promote wound closure.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Waugh HV, Sherratt JA. (2007) - version=1.0
The original CellML model was created by:
Catherine Lloyd
c.lloyd@auckland.ac.nz
The University of Auckland
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL1006230106 | BioModels
Project description:This a model from the article:
Modeling the effects of treating diabetic wounds with engineered skin
substitutes.
Waugh HV, Sherratt JA. Wound Repair Regen
2007 Jul-Aug;15(4):556-65 17650100
,
Abstract:
In this paper, a novel mathematical model of wound healing in both normal and
diabetic cases is presented, focusing upon the effects of adding two currently
available commercial engineered skin substitute therapies to the wound
(Apligraf) and Dermagraft). Our work extends a previously developed model, which
considers inflammatory and repair macrophage dynamics in normal and diabetic
wound healing. Here, we extend the model to include equations for
platelet-derived growth factor concentration, fibroblast density, collagen
density, and hyaluronan concentration. This enables us to examine the variation
of these components in both normal and diabetic wound healing cases, and to
model the treatment protocols of these therapies. Within the context of our
model, we find that the key component to successful healing in diabetic wounds
is hyaluronan and that the therapies work by increasing the amount of hyaluronan
available in the wound environment. The time-to-healing results correlate with
those observed in clinical trials and the model goes some way to establishing an
understanding of why diabetic wounds do not heal, and how these treatments
affect the diabetic wound environment to promote wound closure.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Waugh HV, Sherratt JA. (2007) - version=1.0
The original CellML model was created by:
Catherine Lloyd
c.lloyd@auckland.ac.nz
The University of Auckland
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL1006230003 | BioModels
Project description:This a model from the article:
Modeling the effects of treating diabetic wounds with engineered skin
substitutes.
Waugh HV, Sherratt JA. Wound Repair Regen
2007 Jul-Aug;15(4):556-65 17650100
,
Abstract:
In this paper, a novel mathematical model of wound healing in both normal and
diabetic cases is presented, focusing upon the effects of adding two currently
available commercial engineered skin substitute therapies to the wound
(Apligraf) and Dermagraft). Our work extends a previously developed model, which
considers inflammatory and repair macrophage dynamics in normal and diabetic
wound healing. Here, we extend the model to include equations for
platelet-derived growth factor concentration, fibroblast density, collagen
density, and hyaluronan concentration. This enables us to examine the variation
of these components in both normal and diabetic wound healing cases, and to
model the treatment protocols of these therapies. Within the context of our
model, we find that the key component to successful healing in diabetic wounds
is hyaluronan and that the therapies work by increasing the amount of hyaluronan
available in the wound environment. The time-to-healing results correlate with
those observed in clinical trials and the model goes some way to establishing an
understanding of why diabetic wounds do not heal, and how these treatments
affect the diabetic wound environment to promote wound closure.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Waugh HV, Sherratt JA. (2007) - version=1.0
The original CellML model was created by:
Catherine Lloyd
c.lloyd@auckland.ac.nz
The University of Auckland
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL1006230099 | BioModels
Project description:This a model from the article:
Modeling the effects of treating diabetic wounds with engineered skin
substitutes.
Waugh HV, Sherratt JA. Wound Repair Regen
2007 Jul-Aug;15(4):556-65 17650100
,
Abstract:
In this paper, a novel mathematical model of wound healing in both normal and
diabetic cases is presented, focusing upon the effects of adding two currently
available commercial engineered skin substitute therapies to the wound
(Apligraf) and Dermagraft). Our work extends a previously developed model, which
considers inflammatory and repair macrophage dynamics in normal and diabetic
wound healing. Here, we extend the model to include equations for
platelet-derived growth factor concentration, fibroblast density, collagen
density, and hyaluronan concentration. This enables us to examine the variation
of these components in both normal and diabetic wound healing cases, and to
model the treatment protocols of these therapies. Within the context of our
model, we find that the key component to successful healing in diabetic wounds
is hyaluronan and that the therapies work by increasing the amount of hyaluronan
available in the wound environment. The time-to-healing results correlate with
those observed in clinical trials and the model goes some way to establishing an
understanding of why diabetic wounds do not heal, and how these treatments
affect the diabetic wound environment to promote wound closure.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Waugh HV, Sherratt JA. (2007) - version=1.0
The original CellML model was created by:
Catherine Lloyd
c.lloyd@auckland.ac.nz
The University of Auckland
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL1006230102 | BioModels
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 dbdb 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 TGF/NFB 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.
2024-08-07 | MSV000095545 | MassIVE
Project description:Diabetic foot ulcers (DFUs) are a devastating complication of diabetes. In order to identify systemic and local factors associated with DFU healing, we examined the cellular landscape of DFUs by single-cell RNA-seq analysis of foot and forearm skin specimens, as well as PBMC samples, from 10 non-diabetic subjects, and 17 diabetic patients, 11 with, and 6 without DFU. Our analysis shows enrichment of a unique inflammatory fibroblast population in DFU patients with healing wounds. The patients with healing DFUs also depicted enrichment of macrophages with M1 polarization, as opposed to more M2 macrophages in non-healing wounds. These findings were verified using Immunohistochemistry and Spatial Transcriptomics.
2021-11-01 | GSE165816 | GEO
Project description:Chronic wounds are a common and costly complication of diabetes, where multifactorial defects contribute to dysregulated skin repair, inflammation, tissue damage, and infection. We previously showed that aspects of the diabetic foot ulcer microbiota were correlated with poor healing outcomes, but many microbial species recovered remain uninvestigated with respect to wound healing. Here we focused onAlcaligenes faecalis, a Gram-negative bacterium that is frequently recovered from chronic wounds but rarely causes infection. Treatment of diabetic wounds withA. faecalisaccelerated healing during early stages. We investigated the underlying mechanisms and found thatA. faecalistreatment promotes re-epithelialization of diabetic keratinocytes, a process which is necessary for healing but deficient in chronic wounds. Overexpression of matrix metalloproteinases in diabetes contributes to failed epithelialization, and we found thatA. faecalistreatment balances this overexpression to allow proper healing. This work uncovers a mechanism of bacterial-driven wound repair and provides a foundation for the development of microbiota-based wound interventions.
2024-03-30 | GSE261418 | GEO