Tight Skin 2 Mice Exhibit Delayed Wound Healing Caused by Increased Elastic Fibers in Fibrotic Skin.

Abstract:

:Rationale: The Tight Skin 2 (Tsk2) mouse model of systemic sclerosis (SSc) has many features of human disease, including tight skin, excessive collagen deposition, alterations in the extracellular matrix (ECM), increased elastic fibers, and occurrence of antinuclear antibodies with age. A tight skin phenotype is observed by 2 weeks of age, but measurable skin fibrosis is only apparent at 10 weeks. We completed a series of wound healing experiments to determine how fibrosis affects wound healing in Tsk2/+ mice compared with their wild-type (WT) littermates. Method: We performed these experiments by introducing four 4 mm biopsy punched wounds on the back of each mouse, ventral of the midline, and observed wound healing over 10 days. Tsk2/+ mice showed significantly delayed wound healing and increased wound size compared with the WT littermates at both 5 and 10 weeks of age. We explored the potential sources of this response by wounding Tsk2/+ mice that were genetically deficient either for the NLRP3 inflammasome (a known fibrosis mediator), or for elastic fibers in the skin, using a fibulin-5 knockout. Conclusion: We found that the loss of elastic fibers restores normal wound healing in the Tsk2/+ mouse and that the loss of the NLRP3 inflammasome had no effect. We conclude that elastic fiber dysregulation is the primary cause of delayed wound healing in the Tsk2/+ mouse and therapies that promote collagen deposition in the tissue matrix in the absence of elastin deposition might be beneficial in promoting wound healing in SSc and other diseases.

journal_title

Advances in wound care

authors

Long KB,Burgwin CM,Huneke R,Artlett CM,Blankenhorn EP

doi

10.1089/wound.2014.0529

subject

Has Abstract

pub_date

2014-09-01 00:00:00

pages

573-581

issue

9

eissn

2162-1918

issn

2162-1934

pii

10.1089/wound.2014.0529

journal_volume

3

pub_type

杂志文章
  • Evidence-Based Review of Antibiofilm Agents for Wound Care.

    abstract::Significance: Biofilms in vivo are small densely packed aggregations of microbes that are highly resistant to host immune responses and treatment. They attach to each other and to nearby surfaces. Biofilms are difficult to study and identify in a clinical setting as their quantification necessitates the use of advance...

    journal_title:Advances in wound care

    pub_type: 杂志文章

    doi:10.1089/wound.2020.1193

    authors: Weigelt MA,McNamara SA,Sanchez D,Hirt PA,Kirsner RS

    更新日期:2021-01-01 00:00:00

  • Therapeutic Applications of Extracellular Matrix.

    abstract::Chronic and hard-to-heal wounds are a tremendous burden on our healthcare system and impair the quality of life for millions of people. An emerging focus of regenerative medicine is the development of natural biomaterials that can stimulate tissue formation or repair by recreating the functional and structural propert...

    journal_title:Advances in wound care

    pub_type: 杂志文章

    doi:10.1089/wound.2015.0652

    authors: Hocking DC

    更新日期:2015-08-01 00:00:00

  • Adipose-Derived Regenerative Cell Therapy for Burn Wound Healing: A Comparison of Two Delivery Methods.

    abstract::Objective: The use of noncultured autologous stromal vascular fraction or clinical grade adipose-derived regenerative cells (ADRCs) is a promising strategy to promote wound healing and tissue repair. Nevertheless, issues regarding the optimal mode of administration remain unclear. The purpose of this study was to comp...

    journal_title:Advances in wound care

    pub_type: 杂志文章

    doi:10.1089/wound.2015.0672

    authors: Foubert P,Gonzalez AD,Teodosescu S,Berard F,Doyle-Eisele M,Yekkala K,Tenenhaus M,Fraser JK

    更新日期:2016-07-01 00:00:00

  • Association Between Microbial Bioburden and Healing Outcomes in Venous Leg Ulcers: A Review of the Evidence.

    abstract::Significance: Venous leg ulcers (VLUs) are susceptible to microbial invasion, and serious complications can result without the timely control of infection. Diagnosis of wound infection is primarily based on subjective clinical characteristics and patient-reported symptoms, and the treatment with antimicrobials has not...

    journal_title:Advances in wound care

    pub_type: 评审

    doi:10.1089/wound.2014.0535

    authors: Tuttle MS

    更新日期:2015-01-01 00:00:00

  • Adjustability and Adaptability Are Critical Characteristics of Pediatric Support Surfaces.

    abstract::Significance: Pressure ulcers (PUs) in newborns and children are remarkably different from those in adults, both in their possible causal factors and in the etiology and biomechanical pathways for tissue damage. Recent Advances: Pediatric muscle and fat tissue structures are overall softer than those of adults, making...

    journal_title:Advances in wound care

    pub_type: 杂志文章,评审

    doi:10.1089/wound.2015.0639

    authors: Levy A,Kopplin K,Gefen A

    更新日期:2015-10-01 00:00:00

  • An Improved Humanized Mouse Model for Excisional Wound Healing Using Double Transgenic Mice.

    abstract::Objective: Splinting full-thickness cutaneous wounds in mice has allowed for a humanized model of wound healing. Delineating the epithelial edge and assessing time to closure of these healing wounds via macroscopic visualization have remained a challenge. Approach: Double transgenic mice were created by crossbreeding ...

    journal_title:Advances in wound care

    pub_type: 杂志文章

    doi:10.1089/wound.2017.0772

    authors: Hu MS,Cheng J,Borrelli MR,Leavitt T,Walmsley GG,Zielins ER,Hong WX,Cheung ATM,Duscher D,Maan ZN,Irizarry DM,Stephan B,Parsa FD,Wan DC,Gurtner GC,Lorenz HP,Longaker MT

    更新日期:2018-01-01 00:00:00

  • Therapeutic Approaches to the Regulation of Wound Angiogenesis.

    abstract:SIGNIFICANCE:Re-establishment of a functional vascular network is a critical component of successful wound repair. One of the most potent pro-angiogenic agents is vascular endothelial growth factor (VEGF), which, from a basic science and pre-clinical perspective, seems ideal for the therapeutic stimulation of blood ves...

    journal_title:Advances in wound care

    pub_type: 评审

    doi:10.1089/wound.2011.0348

    authors: Wietecha MS,DiPietro LA

    更新日期:2013-04-01 00:00:00

  • Ovine-Based Collagen Matrix Dressing: Next-Generation Collagen Dressing for Wound Care.

    abstract::Significance: Broad-spectrum metalloproteinase (MMP) reduction along with inherent aspects of an extracellular matrix (ECM) dressing can bring about improved wound healing outcomes and shorter treatment duration. Initial reports of clinical effectiveness of a new ovine-based collagen extracellular matrix (CECM) dressi...

    journal_title:Advances in wound care

    pub_type: 杂志文章,评审

    doi:10.1089/wound.2015.0660

    authors: Bohn G,Liden B,Schultz G,Yang Q,Gibson DJ

    更新日期:2016-01-01 00:00:00

  • Skin Biomechanics and miRNA Expression Following Chronic UVB Irradiation.

    abstract::Objective: Exposure to ultraviolet (UV) light from the sun is known to accelerate the skin aging process and leads to significant alterations in skin biomechanics; however, the molecular mechanisms by which chronic UVB affects biomechanical properties of the skin have not been well described. Approach: A murine model ...

    journal_title:Advances in wound care

    pub_type: 杂志文章

    doi:10.1089/wound.2019.1034

    authors: Blackstone BN,Wilgus TA,Roy S,Wulff BC,Powell HM

    更新日期:2020-03-01 00:00:00

  • Cutaneous Manifestations of COVID-19: A Systematic Review.

    abstract::Objective: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a pandemic. Although pulmonary health has been the primary focus of studies during the early days of COVID-19, development of a comprehensive understanding of this emergent disease requi...

    journal_title:Advances in wound care

    pub_type: 杂志文章

    doi:10.1089/wound.2020.1309

    authors: Singh H,Kaur H,Singh K,Sen CK

    更新日期:2021-02-01 00:00:00

  • Chemokine Involvement in Fetal and Adult Wound Healing.

    abstract::Significance: Fetal wounds heal with a regenerative phenotype that is indistinguishable from surrounding skin with restored skin integrity. Compared to this benchmark, all postnatal wound healing is impaired and characterized by scar formation. The biologic basis of the fetal regenerative phenotype can serve as a road...

    journal_title:Advances in wound care

    pub_type: 杂志文章,评审

    doi:10.1089/wound.2014.0564

    authors: Balaji S,Watson CL,Ranjan R,King A,Bollyky PL,Keswani SG

    更新日期:2015-11-01 00:00:00

  • Autologous Bone Marrow Aspirate Therapy for Skin Tissue Engineering and Tissue Regeneration.

    abstract::Introduction: Chronic wounds that are difficult to heal are physical and financial burden to the sufferer and a challenge to the treating physician. Objective: The main purpose of this study was to develop a novel method of using bone marrow (BM) aspirate, either cultured or fresh, as early solution for healing of chr...

    journal_title:Advances in wound care

    pub_type: 杂志文章

    doi:10.1089/wound.2016.0704

    authors: Gupta GJ,Karki K,Jain P,Saxena AK

    更新日期:2017-04-01 00:00:00

  • Full-Thickness Thermal Injury Delays Wound Closure in a Murine Model.

    abstract::Objective: The contemporary treatment of a full-thickness burn consists of early eschar excision followed by immediate closure of the open wound using autologous skin. However, most animal models study burn wound healing with the persistence of the burn eschar. Our goal is to characterize a murine model of burn eschar...

    journal_title:Advances in wound care

    pub_type: 杂志文章

    doi:10.1089/wound.2014.0570

    authors: Wu JC,Rose LF,Christy RJ,Leung KP,Chan RK

    更新日期:2015-02-01 00:00:00

  • Hypoxic Culturing Enhances the Wound-Healing Potential of Adipose-Derived Stem Cells.

    abstract:BACKGROUND:Adipose tissue is one of the richest sources of mesenchymal stem cells that exhibit an outstanding ability to regenerate skin. THE PROBLEM:Although the anatomical sites of adipose-derived stem cells (ASCs) in the body are relatively oxygen-deficient (i.e., 1%-5% oxygen content), ASCs are usually cultured un...

    journal_title:Advances in wound care

    pub_type: 评审

    doi:10.1089/wound.2011.0312

    authors: Kim WS,Sung JH

    更新日期:2012-08-01 00:00:00

  • Mathematical Modeling Can Advance Wound Healing Research.

    abstract::Significance: For over 30 years, there has been sustained interest in the development of mathematical models for investigating the complex mechanisms underlying each stage of the wound healing process. Despite the immense associated challenges, such models have helped usher in a paradigm shift in wound healing researc...

    journal_title:Advances in wound care

    pub_type: 杂志文章

    doi:10.1089/wound.2019.1132

    authors: Menon SN,Flegg JA

    更新日期:2020-09-11 00:00:00

  • Toll-Like Receptor Signaling in Burn Wound Healing and Scarring.

    abstract::Significance: Damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) emanate from burn-injured tissue and enter systemic circulation. Locally and systemically, they activate pattern-recognition receptors, including toll-like receptors (TLRs), to stimulate cytokine secretion, wh...

    journal_title:Advances in wound care

    pub_type: 杂志文章,评审

    doi:10.1089/wound.2017.0733

    authors: D'Arpa P,Leung KP

    更新日期:2017-10-01 00:00:00

  • Instillation Negative Pressure Wound Therapy: A Role for Infected LVAD Salvage.

    abstract::Objective: To determine the utility of instillation negative pressure wound therapy (NPWT) in achieving eradication of infection and definitive wound closure in patients with infected left ventricular assist device (LVAD). Approach: A retrospective review was performed in a series of patients with infected and exposed...

    journal_title:Advances in wound care

    pub_type: 杂志文章

    doi:10.1089/wound.2018.0832

    authors: Hodson T,West JM,Poteet SJ,Lee PH,Valerio IL

    更新日期:2019-03-01 00:00:00

  • In Vitro and Ex Vivo Models for Functional Testing of Therapeutic Anti-scarring Drug Targets in Keloids.

    abstract::Significance: Keloids are benign fibro-proliferative raised dermal lesions that spread beyond the original borders of the wound, continue to grow, rarely regress, and are the most common in pigmented individuals after an abnormal wound healing response. The current treatment failure and respective challenges involved ...

    journal_title:Advances in wound care

    pub_type: 杂志文章,评审

    doi:10.1089/wound.2019.1040

    authors: Sharma JR,Lebeko M,Kidzeru EB,Khumalo NP,Bayat A

    更新日期:2019-12-01 00:00:00

  • The Wound Microbiome: Modern Approaches to Examining the Role of Microorganisms in Impaired Chronic Wound Healing.

    abstract::Significance: Bacterial burden is believed to play a significant role in impaired wound healing of chronic wounds and the development of infection-related complications. The standard of care in the clinic relies upon cultivation-dependent methods to identify microorganisms. These assays are biased toward microorganism...

    journal_title:Advances in wound care

    pub_type: 评审

    doi:10.1089/wound.2012.0397

    authors: Misic AM,Gardner SE,Grice EA

    更新日期:2014-07-01 00:00:00

  • Three-Dimensional Printing and Cell Therapy for Wound Repair.

    abstract::Significance: Skin tissue damage is a major challenge and a burden on healthcare systems, from burns and other trauma to diabetes and vascular disease. Although the biological complexities are relatively well understood, appropriate repair mechanisms are scarce. Three-dimensional bioprinting is a layer-based approach ...

    journal_title:Advances in wound care

    pub_type: 杂志文章,评审

    doi:10.1089/wound.2017.0752

    authors: van Kogelenberg S,Yue Z,Dinoro JN,Baker CS,Wallace GG

    更新日期:2018-05-01 00:00:00

  • Focal Contact and Hemidesmosomal Proteins in Keratinocyte Migration and Wound Repair.

    abstract::Significance: During wound healing of the skin, keratinocytes should move over while still adhering to their underlying matrix. Thus, mechanistic insights into the wound-healing process require an understanding of the forms and functions of keratinocyte matrix adhesions, specifically focal contacts and hemidesmosomes,...

    journal_title:Advances in wound care

    pub_type: 评审

    doi:10.1089/wound.2013.0489

    authors: Hopkinson SB,Hamill KJ,Wu Y,Eisenberg JL,Hiroyasu S,Jones JC

    更新日期:2014-03-01 00:00:00

  • Human Wound-Healing Research: Issues and Perspectives for Studies Using Wide-Scale Analytic Platforms.

    abstract::Significance: Revealing the basic mechanisms in the healing process and then regulating these processes for faster healing or to avoid negative outcomes such as infection or scarring are fundamental to wound research. The normal healing process is basically known, but to thoroughly understand the very complex aspects ...

    journal_title:Advances in wound care

    pub_type: 评审

    doi:10.1089/wound.2013.0502

    authors: Nuutila K,Katayama S,Vuola J,Kankuri E

    更新日期:2014-03-01 00:00:00

  • Current Advancements and Strategies in Tissue Engineering for Wound Healing: A Comprehensive Review.

    abstract::Significance: With an aging population leading to an increase in diabetes and associated cutaneous wounds, there is a pressing clinical need to improve wound-healing therapies. Recent Advances: Tissue engineering approaches for wound healing and skin regeneration have been developed over the past few decades. A review...

    journal_title:Advances in wound care

    pub_type: 杂志文章,评审

    doi:10.1089/wound.2016.0723

    authors: Ho J,Walsh C,Yue D,Dardik A,Cheema U

    更新日期:2017-06-01 00:00:00

  • Effect of Flightless I Expression on Epidermal Stem Cell Niche During Wound Repair.

    abstract::Objective: Activation of epidermal stem cells (EpSCs) from their quiescent niche is an integral component of wound reepithelialization and involves Wnt/β-catenin (β-Cat) signaling and remodeling of the actin cytoskeleton. The aim of this study was to investigate the effect of Flightless I (Flii), a cytoskeletal protei...

    journal_title:Advances in wound care

    pub_type: 杂志文章

    doi:10.1089/wound.2018.0884

    authors: Yang GN,Strudwick XL,Bonder C,Kopecki Z,Cowin AJ

    更新日期:2020-04-01 00:00:00

  • Safety and Feasibility of Intermittent Electrical Stimulation for the Prevention of Deep Tissue Injury.

    abstract::Objective: To investigate the safety, feasibility, and acceptability of a novel treatment, intermittent electrical stimulation (IES), for preventing deep tissue injury (DTI) in different healthcare settings. Approach: Testing was conducted in an acute rehabilitation unit of a general hospital, a tertiary rehabilitatio...

    journal_title:Advances in wound care

    pub_type: 杂志文章

    doi:10.1089/wound.2014.0569

    authors: Ahmetović A,Mushahwar VK,Sommer R,Schnepf D,Kawasaki L,Warwaruk-Rogers R,Barlott T,Chong SL,Isaacson G,Kim S,Ferguson-Pell M,Stein RB,Ho C,Dukelow S,Chan KM

    更新日期:2015-03-01 00:00:00

  • Medicare Coverage: You Cannot Play the Game If You Do Not Know the Rules.

    abstract::WOUND CARE STAKEHOLDERS SHOULD REMEMBER THAT MEDICARE REIMBURSEMENT REQUIRES THREE PARTS: a relevant code, a published Medicare payment rate, and positive coverage or coverage based upon medical necessity. Qualified healthcare professionals, scientists, and manufacturers should establish a monthly routine, where they ...

    journal_title:Advances in wound care

    pub_type: 杂志文章

    doi:10.1089/wound.2013.0498

    authors: Schaum KD

    更新日期:2013-12-01 00:00:00

  • Impact of Traumatic Lower Extremity Injuries Beyond Acute Care: Movement-Based Considerations for Resultant Longer Term Secondary Health Conditions.

    abstract::Significance: Advances in field-based trauma care, surgical techniques, and protective equipment have collectively facilitated the survival of a historically large number of service members (SMs) following combat trauma, although many sustained significant composite tissue injuries to the extremities, including limb l...

    journal_title:Advances in wound care

    pub_type: 杂志文章,评审

    doi:10.1089/wound.2016.0714

    authors: Butowicz CM,Dearth CL,Hendershot BD

    更新日期:2017-08-01 00:00:00

  • Proteases and Delayed Wound Healing.

    abstract:SIGNIFICANCE:Proteases and their inhibitors contribute to the balance between extracellular matrix (ECM) degradation and deposition, creating an equilibrium that is essential for the timely and coordinated healing of cutaneous wounds. However, when this balance is disrupted, wounds are led into a state of chronicity ch...

    journal_title:Advances in wound care

    pub_type: 评审

    doi:10.1089/wound.2012.0370

    authors: McCarty SM,Percival SL

    更新日期:2013-10-01 00:00:00

  • A Viable Lyopreserved Amniotic Membrane Modulates Diabetic Wound Microenvironment and Accelerates Wound Closure.

    abstract::Objective: Wound healing is a complex process involving the dynamic interplay of various types of cells and bioactive factors. Impaired wound healing is characterized by a loss in synchronization of the process, resulting in non-healing chronic wounds. Human amniotic membrane (AM) has been shown to be effective in the...

    journal_title:Advances in wound care

    pub_type: 杂志文章

    doi:10.1089/wound.2018.0931

    authors: Dhall S,Hoffman T,Sathyamoorthy M,Lerch A,Jacob V,Moorman M,Kuang JQ,Danilkovitch A

    更新日期:2019-08-01 00:00:00

  • Oxygen: Implications for Wound Healing.

    abstract:BACKGROUND:Oxygen is vital for healing wounds. It is intricately involved in numerous biological processes including cell proliferation, angiogenesis, and protein synthesis, which are required for restoration of tissue function and integrity. Adequate wound tissue oxygenation can trigger healing responses and favorably...

    journal_title:Advances in wound care

    pub_type: 评审

    doi:10.1089/wound.2011.0319

    authors: Castilla DM,Liu ZJ,Velazquez OC

    更新日期:2012-12-01 00:00:00