scholarly journals Principles of Cell Circuits for Tissue Repair and Fibrosis

2019 ◽  
Author(s):  
Miri Adler ◽  
Avi Mayo ◽  
Xu Zhou ◽  
Ruth Franklin ◽  
Matthew Meizlish ◽  
...  
Keyword(s):  
Wound Healing ◽  
Tissue Repair ◽  
Time Window ◽  
Pathological State ◽  
Protective Response ◽  
Dynamic Mechanisms ◽  
Normal Wound Healing ◽  
A Cell ◽  
Cell Circuit ◽  
Scar Maturation

AbstractTissue-repair is a protective response after injury, but repetitive or prolonged injury can lead to fibrosis, a pathological state of excessive scarring. To pinpoint the dynamic mechanisms underlying fibrosis, it is important to understand the principles of the cell circuits that carry out tissue-repair. In this study, we establish a cell-circuit framework for the myofibroblast-macrophage circuit in wound-healing, including the accumulation of scar-forming extracellular matrix. We find that fibrosis results from multistability between three outcomes, which we term ‘hot fibrosis’ characterized by many macrophages, ‘cold fibrosis’ lacking macrophages, and normal wound-healing. The cell-circuit framework clarifies several unexplained phenomena including the paradoxical effect of macrophage depletion, the limited time-window in which removing inflammation leads to healing, the effects of cellular senescence, and why scar maturation takes months. We define key parameters that control the transition from healing to fibrosis, which may serve as potential targets for therapeutic reduction of fibrosis.

scholarly journals Topical steroids for chronic wounds displaying abnormal inflammation

2013 ◽  
Vol 95 (4) ◽  
pp. 291-296 ◽  
Author(s):  
DC Bosanquet ◽  
A Rangaraj ◽  
AJ Richards ◽  
A Riddell ◽  
VM Saravolac ◽  
...  
Keyword(s):  
Wound Healing ◽  
Tissue Repair ◽  
Chronic Wounds ◽  
Treatment Time ◽  
Topical Steroid ◽  
Symptom Burden ◽  
Topical Steroids ◽  
Normal Wound Healing ◽  
Healing Wounds

Introduction Chronic, non-healing wounds are often characterised by an excessive, and detrimental, inflammatory response. We review our experience of using a combined topical steroid, antibiotic and antifungal preparation in the treatment of chronic wounds displaying abnormal and excessive inflammation. Methods A retrospective review was undertaken of all patients being treated with a topical preparation containing a steroid (clobetasone butyrate 0.05%), antibiotic and antifungal at a tertiary wound healing centre over a ten-year period. Patients were selected as the primary treating physician felt the wounds were displaying excessive inflammation. Healing rates were calculated for before and during this treatment period for each patient. Changes in symptom burden (pain, odour and exudate levels) following topical application were also calculated. Results Overall, 34 ulcers were identified from 25 individual patients (mean age: 65 years, range: 37–97 years) and 331 clinic visits were analysed, spanning a total time of 14,670 days (7,721 days ‘before treatment’ time, 6,949 days ‘during treatment’ time). Following treatment, 24 ulcers demonstrated faster rates of healing, 3 ulcers showed no significant change in healing rates and 7 were healing more slowly (p=0.0006). Treatment generally reduced the burden of pain and exudate, without affecting odour. Conclusions In normal wound healing, inflammation represents a transient but essential phase of tissue repair. In selected cases, direct application of a steroid containing agent has been shown to improve healing rates, presumably by curtailing this phase. Further evaluation is required to establish the role of preparations containing topical steroids without antimicrobials in the management of chronic wounds.

scholarly journals The initiation of the wound healing program is regulated by the convergence of mechanical and epigenetic cues

2021 ◽  
Author(s):  
Tanay Bhatt ◽  
Akshay Hegde ◽  
Rakesh Dey ◽  
Alhad Ketkar ◽  
Ajai Pulianmackal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Wound Healing ◽  
Tissue Repair ◽  
Dna Methyltransferase ◽  
Nuclear Translocation ◽  
Repair Process ◽  
Cellular Reprogramming ◽  
Cellular Behavior ◽  
A Cell ◽  
Signaling Modules

Wound healing in the skin is a complex physiological process that is a product of a cell state transition from homeostasis to repair. Mechanical cues are increasingly being recognized as important regulators of cellular reprogramming, but the mechanism by which it is translated to changes in gene expression and ultimately cellular behavior remains largely a mystery. To probe the molecular underpinnings of this phenomenon further, we used the downregulation of caspase-8 as a biomarker of a cell entering the wound-healing program. We found that the wound-induced release of tension within the epidermis leads to the alteration of gene expression via the nuclear translocation of the DNA methyltransferase 3A (DNMT3a). This enzyme then methylates promoters of genes that are known to be downregulated in response to wound stimuli as well as potentially novel players in the repair program. Overall, these findings illuminate the convergence of mechanical and epigenetic signaling modules that are important regulators of the transcriptome landscape required to initiate the tissue repair process in the differentiated layers of the epidermis.

Solid emulsion gel as a vehicle for delivery of polyunsaturated fatty acids: implications for tissue repair, dermal angiogenesis and wound healing

2008 ◽  
Vol 2 (7) ◽  
pp. 383-393 ◽  
Author(s):  
Kirill I. Shingel ◽  
Marie-Pierre Faure ◽  
Laurent Azoulay ◽  
Christophe Roberge ◽  
Richard J. Deckelbaum
Keyword(s):  
Fatty Acids ◽  
Wound Healing ◽  
Polyunsaturated Fatty Acids ◽  
Tissue Repair ◽  
Emulsion Gel

scholarly journals Squalene Stimulates a Key Innate Immune Cell to Foster Wound Healing and Tissue Repair

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Cristina Sánchez-Quesada ◽  
Alicia López-Biedma ◽  
Estefania Toledo ◽  
José J. Gaforio
Keyword(s):  
Wound Healing ◽  
Inflammatory Cytokines ◽  
Tissue Repair ◽  
Immune Cell ◽  
Critical Role ◽  
Virgin Olive Oil ◽  
Skin Damage ◽  
Macrophage Response ◽  
Anti Inflammatory ◽  
Minor Compounds

Anti-inflammatory effects of virgin olive oil (VOO) have been described recently, along with its wound healing effect. One of the main minor compounds found in VOO is squalene (SQ), which also possesses preventive effects against skin damage and anti-inflammatory properties. The inflammatory response is involved in wound healing and manages the whole process by macrophages, among others, as the main innate cells with a critical role in the promotion and resolution of inflammation for tissue repair. Because of that, this work is claimed to describe the role that squalene exerts in the immunomodulation of M1 proinflammatory macrophages, which are the first cells implicate in recent injuries. Pro- and anti-inflammatory cytokines were analysed using TPH1 cell experimental model. SQ induced an increase in the synthesis of anti-inflammatory cytokines, such as IL-10, IL-13, and IL-4, and a decrease in proinflammatory signals, such as TNF-α and NF-κB in M1 proinflammatory macrophages. Furthermore, SQ enhanced remodelling and repairing signals (TIMP-2) and recruitment signals of eosinophils and neutrophils, responsible for phagocytosis processes. These results suggest that SQ is able to promote wound healing by driving macrophage response in inflammation. Therefore, squalene could be useful at the resolution stage of wound healing.

Thrombin and Thrombin Peptides in Wound Healing and Tissue Repair

Thrombin ◽  
2008 ◽  
pp. 115-132 ◽  
Author(s):  
Barbara Olszewska-Pazdrak ◽  
John S. Bergmann ◽  
Gerald M. Fuller ◽  
Darrell H. Carney
Keyword(s):  
Wound Healing ◽  
Tissue Repair

Human Trophoblast: A Biological and Clinical Demonstration of its Wound Healing and Tissue Repair Properties

1989 ◽  
pp. 161-171
Author(s):  
Olga Genbačev ◽  
Jasna Lesić ◽  
Dragica Ljuština ◽  
S. Mičić ◽  
Nada Papić ◽  
...  
Keyword(s):  
Wound Healing ◽  
Tissue Repair ◽  
Human Trophoblast

scholarly journals Adenosine Diphosphate Improves Wound Healing in Diabetic Mice Through P2Y12 Receptor Activation

2021 ◽  
Vol 12 ◽  
Author(s):  
Paula Alvarenga Borges ◽  
Ingrid Waclawiak ◽  
Janaína Lima Georgii ◽  
Vanderlei da Silva Fraga-Junior ◽  
Janaína Figueiredo Barros ◽  
...  
Keyword(s):  
Wound Healing ◽  
T Cells ◽  
Receptor Antagonist ◽  
Tissue Repair ◽  
Cellular Response ◽  
Chronic Wounds ◽  
Γδ T Cells ◽  
Receptor Activation ◽  
Skin Wounds ◽  
Diabetic Mice

Chronic wounds are a public health problem worldwide, especially those related to diabetes. Besides being an enormous burden to patients, it challenges wound care professionals and causes a great financial cost to health system. Considering the absence of effective treatments for chronic wounds, our aim was to better understand the pathophysiology of tissue repair in diabetes in order to find alternative strategies to accelerate wound healing. Nucleotides have been described as extracellular signaling molecules in different inflammatory processes, including tissue repair. Adenosine-5’-diphosphate (ADP) plays important roles in vascular and cellular response and is immediately released after tissue injury, mainly from platelets. However, despite the well described effect on platelet aggregation during inflammation and injury, little is known about the role of ADP on the multiple steps of tissue repair, particularly in skin wounds. Therefore, we used the full-thickness excisional wound model to evaluate the effect of local ADP application in wounds of diabetic mice. ADP accelerated cutaneous wound healing, improved new tissue formation, and increased both collagen deposition and transforming growth factor-β (TGF-β) production in the wound. These effects were mediated by P2Y12 receptor activation since they were inhibited by Clopidogrel (Clop) treatment, a P2Y12 receptor antagonist. Furthermore, P2Y1 receptor antagonist also blocked ADP-induced wound closure until day 7, suggesting its involvement early in repair process. Interestingly, ADP treatment increased the expression of P2Y12 and P2Y1 receptors in the wound. In parallel, ADP reduced reactive oxygen species (ROS) formation and tumor necrosis factor-α (TNF-α) levels, while increased IL-13 levels in the skin. Also, ADP increased the counts of neutrophils, eosinophils, mast cells, and gamma delta (γδ) T cells (Vγ4+ and Vγ5+ cells subtypes of γδ+ T cells), although reduced regulatory T (Tregs) cells in the lesion. In accordance, ADP increased fibroblast proliferation and migration, myofibroblast differentiation, and keratinocyte proliferation. In conclusion, we provide strong evidence that ADP acts as a pro-resolution mediator in diabetes-associated skin wounds and is a promising intervention target for this worldwide problem.

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