The browning and mobilization of subcutaneous white adipose tissue supports efficient skin repair
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE247964 | GEO | 2023/11/21
REPOSITORIES: GEO
Similar Datasets
Project description:Proteinases play a pivotal role in wound healing by degrading molecular barriers, regulating cell-matrix interactions and availability of bioactive molecules. Matrix metalloproteinase-13 (MMP-13, collagenase-3) is a wide spectrum proteinase. Its expression and function is linked to the growth and invasion of many epithelial cancers such as squamous cell carcinoma. Moreover, the physiologic expression of MMP-13 is associated e.g. to scarless healing of human fetal skin and adult gingival wounds. While MMP-13 is not found in the normally healing skin wounds in human adults, it is expressed in mouse skin during wound healing. Thus, mouse wound healing models can be utilized for studying the role of MMP-13 in the events of wound healing. As the processes such as the migration and proliferation of keratinocytes, angiogenesis, inflammation and activation of fibroblasts are components of wound repair as well as of cancer, many results received from wound healing studies are also adaptable to cancer research. Classically, the process of wound healing can be devided into three phases which are histologically and functionally separate but temporally overlapping: 1) hemostasis and inflammation, 2) re-epithelialization and granulation tissue formation, and 3) matrix remodeling. Granulation tissue is formed into the wound via fibroplasia, angiogenesis and extracellular matrix (ECM) deposition by fibroblasts. Granulation tissue is rich in inflammatory cells, fibroblasts, myofibroblasts and blood vessels. After epidermal recovery, the granulation tissue is resolved via matrix remodeling and cell apoptosis. A sterile viscose cellulose sponge (VCS) characterized by defined size and structure can be used to experimentally induce formation of subcutaneous granulation tissue. Compared to normal granulation tissue, this model allows easy examination of the granulation tissue in its entirety but leaving out epidermal keratinocytes in the sample preparation. In this study, we studied the role of MMP-13 in the formation of mouse VCS-induced granulation tissue. We performed gene expression profiling of the granulation tissue samples of Mmp13-/- (KO) and wild type (WT) mice harvested at day 7, day 14 and day 21 after VCS implantation. Mmp13-/- (KO) mice were generated as described (Inada et al. 2004, PNAS, 101: 17192-17197) and used in these experiments after backcrossing at least seven generations into C57BL6 mice. The WT mice were generated from the backcrossed heterozygote Mmp13-/- (KO) mice. Granulation tissues were harvested at three time points (7d, 14d, 21d) from Mmp13-/- (KO) and WT mice. One sample of each mouse was analyzed (n=3, 7d; n=4, 14d; n=4, 21d; for each genotype). The samples were processed for RNA extraction and Affymetrix 3'IVT DNA microarray gene expression analysis.
2012-08-07 | E-GEOD-38822 | biostudies-arrayexpress
Project description:Proteinases play a pivotal role in wound healing by degrading molecular barriers, regulating cell-matrix interactions and availability of bioactive molecules. Matrix metalloproteinase-13 (MMP-13, collagenase-3) is a wide spectrum proteinase. Its expression and function is linked to the growth and invasion of many epithelial cancers such as squamous cell carcinoma. Moreover, the physiologic expression of MMP-13 is associated e.g. to scarless healing of human fetal skin and adult gingival wounds. While MMP-13 is not found in the normally healing skin wounds in human adults, it is expressed in mouse skin during wound healing. Thus, mouse wound healing models can be utilized for studying the role of MMP-13 in the events of wound healing. As the processes such as the migration and proliferation of keratinocytes, angiogenesis, inflammation and activation of fibroblasts are components of wound repair as well as of cancer, many results received from wound healing studies are also adaptable to cancer research. Classically, the process of wound healing can be devided into three phases which are histologically and functionally separate but temporally overlapping: 1) hemostasis and inflammation, 2) re-epithelialization and granulation tissue formation, and 3) matrix remodeling. Granulation tissue is formed into the wound via fibroplasia, angiogenesis and extracellular matrix (ECM) deposition by fibroblasts. Granulation tissue is rich in inflammatory cells, fibroblasts, myofibroblasts and blood vessels. After epidermal recovery, the granulation tissue is resolved via matrix remodeling and cell apoptosis. A sterile viscose cellulose sponge (VCS) characterized by defined size and structure can be used to experimentally induce formation of subcutaneous granulation tissue. Compared to normal granulation tissue, this model allows easy examination of the granulation tissue in its entirety but leaving out epidermal keratinocytes in the sample preparation. In this study, we studied the role of MMP-13 in the formation of mouse VCS-induced granulation tissue. We performed gene expression profiling of the granulation tissue samples of Mmp13-/- (KO) and wild type (WT) mice harvested at day 7, day 14 and day 21 after VCS implantation.
2012-08-08 | GSE38822 | GEO
Project description:Although inflammation plays critical roles in the development of atherosclerosis, its regulatory mechanisms remain incompletely understood. Perivascular adipose tissue (PVAT) has been reported to undergo inflammatory changes in response to vascular injury. Here, we showed that vascular injury induced the beiging (brown adipose tissue-like phenotype change) of PVAT, which fine-tunes inflammatory response and thus vascular remodeling as a protective mechanism. In a mouse model of endovascular injury, macrophages accumulated in PVAT, causing beiging phenotype change. Inhibition of PVAT beiging by genetically silencing PRDM16, a key regulator to beiging, exacerbated inflammation and vascular remodeling following injury. Conversely, activation of PVAT beiging attenuated inflammation and pathological vascular remodeling. Single-cell RNA sequencing revealed that beige adipocytes abundantly expressed neuregulin 4 (Nrg4) which critically regulated alternative macrophage activation. Importantly, significant beiging was observed in the diseased aortic PVAT in patients with acute aortic dissection. Taken together, vascular injury induced the beiging of adjacent PVAT with macrophage accumulation, where NRG4 secreted from the beige PVAT facilitated alternative activation of macrophages, leading to the resolution of vascular inflammation. Our study demonstrated the pivotal roles of PVAT in vascular inflammation and remodeling and will open a new avenue for treating atherosclerosis.
2022-06-21 | GSE206399 | GEO
Project description:Defective fibroblast migration cause delayed wound healing (WH) and chronic skin lesions. Autologous micrograft (AMG) therapies have recently emerged as a new effective treatment able to improve wound healing capacity. However, the molecular mechanisms connecting their beneficial outcomes with the wound healing process are still unrevealed. Here, we show that AMG modulates primary fibroblast migration and accelerates skin re-epithelialization without affecting cell proliferation. We demonstrate that AMG is enriched in a pool of WH-associated growth factors that may provide the initiation signal for faster endogenous wound healing response. This, in turn leads to increased cell migration rate by elevating activity of ERK and subsequent activation of matrix metalloproteinase expression and their extracellular enzymatic activity. Moreover, AMG-treated wounds showed increased granulation tissue formation and organized collagen content. Overall, we shed light on AMG molecular mechanism supporting its potential to trigger highly improved wound healing process.
2020-01-01 | GSE123829 | GEO
Project description:Tissue repair processes maintain proper organ function following mechanical or infection related damage. In addition to anti-bacterial properties, MAIT cells express a tissue repair transcriptomic program and promote skin wound healing when expanded. Herein, we use a human‑like full‑thickness skin excision mouse model to assess the underlying mechanisms of MAIT cell tissue repair function. Single-cell RNAseq analysis suggests that skin MAIT cells already express a repair program at steady state. Following skin excision, MAIT cells promote keratinocyte proliferation thereby accelerating healing. Using skin grafts, parabiosis and adoptive transfer experiments, we show that MAIT cells migrate into the wound from other tissues in a TCR independent but CXCR6 dependent manner. Amphiregulin secreted by MAIT cells following excision promotes wound healing. The repair function is independent of sustained TCR stimulation. Overall, our study provides mechanistic insight into MAIT cell wound healing function in the skin.
2023-01-10 | GSE207348 | 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:The present study aimed to delineate the central mechanisms by which androgens delay wound repair. Blocking the conversion of testosterone to 5alpha-dihydrotestosterone (DHT) by 5alpha-reductase limits its ability to impair skin wound healing, suggesting that DHT is a more potent inhibitor of repair than is testosterone. This study aims to identify, through transcription profiling, potential mechanisms by which the 5alpha-reductase inhibitor MK-434 modulates repair. Microarray analysis of wound RNA samples from rats in which the transformation of testosterone to DHT is prevented has identified biological processes and key individual genes through which DHT may contribute to the altered healing profile in such animals. These include genes with putative roles in wound contraction and re-epithelialization.
2009-02-20 | E-MEXP-1232 | biostudies-arrayexpress
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