Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1289895 | ENA |
REPOSITORIES: ENA
Similar Datasets
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:MicroRNAs are powerful gene expression regulators, but their corneal repertoire and potential changes in corneal diseases remain unknown. Our purpose was to identify miRNAs altered in the human diabetic cornea by microarray analysis, and to examine their effects on wound healing in cultured telomerase-immortalized human corneal epithelial cells (HCEC) in vitro. Using microarrays, 29 miRNAs were identified as differentially expressed in diabetic samples. Two miRNA candidates showing the highest fold increased in expression in the diabetic cornea were confirmed by Q-PCR and further characterized. HCEC transfection with h-miR-146a or h-miR-424 significantly retarded wound closure, but their respective antagomirs significantly enhanced wound healing vs. controls. Cells treated with h-miR-146a or h-miR-424 had decreased p-p38 and p-EGFR staining, but these increased over control levels close to the wound edge upon antagomir treatment. In conclusion, several miRNAs with increased expression in human diabetic central corneas were found. Two such miRNAs inhibited cultured corneal epithelial cell wound healing. Dysregulation of miRNA expression in human diabetic cornea may be an important mediator of abnormal wound healing.
2013-11-09 | GSE52233 | GEO
Project description:Impaired wound healing is one of the main reasons that leads to diabetic foot ulcerations. However, the exact mechanism of delayed wound healing in diabetes mellitus is not fully understood. Long non-coding RNAs (lncRNAs) are widely involved in a variety of biological processes and diseases, including diabetes and its associated complications. To further identify the roles of LncRNAs in diabetic wound healing, four STZ induced diabetic rat skin tissues and four control rat skin tissues were prepared for a LncRNAs microarray expression profiling by using rat LncRNA Array (4 x 44K, Arraystar).
2022-09-29 | GSE214338 | GEO
Project description:MicroRNAs are powerful gene expression regulators, but their corneal repertoire and potential changes in corneal diseases remain unknown. Our purpose was to identify miRNAs altered in the human diabetic cornea by microarray analysis, and to examine their effects on wound healing in cultured telomerase-immortalized human corneal epithelial cells (HCEC) in vitro. Using microarrays, 29 miRNAs were identified as differentially expressed in diabetic samples. Two miRNA candidates showing the highest fold increased in expression in the diabetic cornea were confirmed by Q-PCR and further characterized. HCEC transfection with h-miR-146a or h-miR-424 significantly retarded wound closure, but their respective antagomirs significantly enhanced wound healing vs. controls. Cells treated with h-miR-146a or h-miR-424 had decreased p-p38 and p-EGFR staining, but these increased over control levels close to the wound edge upon antagomir treatment. In conclusion, several miRNAs with increased expression in human diabetic central corneas were found. Two such miRNAs inhibited cultured corneal epithelial cell wound healing. Dysregulation of miRNA expression in human diabetic cornea may be an important mediator of abnormal wound healing. Total RNA was extracted from age-matched human autopsy normal (n=6) and diabetic (n=6) central corneas, Flash Tag end-labeled, and hybridized to Affymetrix® GeneChip® miRNA Arrays. Select miRNAs associated with diabetic cornea were validated by quantitative RT-PCR (Q-PCR) and by in situ hybridization (ISH) in independent samples.
2013-11-09 | E-GEOD-52233 | biostudies-arrayexpress
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.
2024-08-13 | GSE274513 | GEO
Project description:Wound healing represents a complex biological process necessitating innovative therapeutic approaches, particularly for chronic wounds such as diabetic foot ulcers (DFUs). Inspired by the regenerative effects of tibial bone transport for DFUs, we explored whether radial extracorporeal shockwave therapy (rESWT) at the tibial circlularr osteotomy site (TOE) could enhance wound healing in rats. We found that TOE accelerated dorsal foot wound healing via small extracellular vesicles (sEV). This sEVs showed strong regenerative effects and modulated macrophage polarizations in vitro and in vivo. Single-cell sequencing revealed mesenchymal stem cells as the likely sEV source, with rESWT triggering sEV release through ATP/P2X7R/p38MAPK pathway. Proteomic analysis identified five differentially expressed proteins in sEVs, with Thbs1-enhanced sEVs enhancing wound healing by promoting IL4-induced M2 macrophage polarization. This innovative approach represents a promising alternative strategy for wound management, with potential for future DFU treatment.
2025-12-30 | GSE314229 | GEO
Project description:At present, there is no effective treatment for diabetic wounds, and the cost of treatment is high. MicroRNAs (miRNAs) plays an important role in the process of diabetic wound healing. By regulating the expression of target genes, it regulates growth factors, cytokines and signal pathways, thereby affecting various stages of ulcer healing such as hemostasis, anti-inflammatory, proliferation and remodeling. In this study, differential expression of miRNAs in diabetic wound was screened. MiR-206 was selected as the research object to detect the effect of miR-206 on the proliferation of fibroblasts and vascular endothelial cell by regulating HIF-1?. Finally, in vivo studies showed that miR-206 antagomir could promote the expression of HIF-1?, CD34 and VEGF, and further promote wound healing in diabetic rats.
2022-11-10 | GSE188783 | 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 | 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