The extracellular matrix of lip wounds in fetal, neonatal and adult mice

Development ◽  
1991 ◽  
Vol 112 (2) ◽  
pp. 651-668
Author(s):  
D.J. Whitby ◽  
M.W. Ferguson
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Cell Migration ◽  
Inflammatory Response ◽  
Cell Function ◽  
Chondroitin Sulphate ◽  
Scar Formation ◽  
Collagen Types ◽  
Cellular Mechanisms ◽  
Collagen Formation

Wound healing in the fetus occurs rapidly, by a regenerative process and without an inflammatory response, resulting in complete restitution of normal tissue function. By contrast, in the adult, wounds heal with scar formation, which may impair function and inhibit further growth. The cellular mechanisms underlying these differing forms of wound healing are unknown but the extracellular matrix (ECM), through its effects on cell function, may play a key role. We have studied the ECM in upper lip wounds of adult, neonatal and fetal mice at days 14, 16 and 18 of gestation. The spatial and temporal distribution of collagen types I, III, IV, V and VI, fibronectin, tenascin, laminin, chondroitin and heparan sulphates were examined immunohistochemically. Results from the fetal groups were essentially similar whilst there were distinct differences between fetus, neonate and adult. Fibronectin was present at the surface of the wound in all groups at 1 h post-wounding. Tenascin was also present at the wound surface but the time at which it was first present differed between fetus (1 h), neonate (12 h) and adult (24 h). The time of first appearance paralleled the rate of wound healing which was most rapid in the fetus and slowest in the adult. Tenascin inhibits the cell adhesion effect of fibronectin and during development the appearance of tenascin correlates with the initiation of cell migration. During wound healing the appearance of tenascin preceded cell migration and the rapid closure of fetal wounds may be due to the early appearance of tenascin in the wound. Collagen types I, III, IV, V and VI were present in all three wound groups but the timing and pattern of collagen deposition differed, with restoration of the normal collagen pattern in the fetus and a scar pattern in the adult. This confirms that lack of scarring in fetal wounds is due to the organisation of collagen within the wound and not simply lack of collagen formation. The distribution of chondroitin sulphate differed between normal fetal and adult tissues and between fetal and adult wounds. Its presence in the fetal wound may alter collagen fibril formation. No inflammatory response was seen in the fetal wounds. The differences in the ECM of fetal and adult wounds suggests that it may be possible to alter the adult wound so that it heals by a fetal-like process without scar formation, loss of tissue function or restriction of growth.

Understanding the mechanisms that determine extracellular matrix remodeling in the infarcted myocardium

2019 ◽  
Vol 47 (6) ◽  
pp. 1679-1687
Author(s):  
Mavis A.A. Tenkorang ◽  
Upendra Chalise ◽  
Michael J. Daseke, II ◽  
Shelby R. Konfrst ◽  
Merry L. Lindsey
Keyword(s):  
Myocardial Infarction ◽  
Extracellular Matrix ◽  
Wound Healing ◽  
Inflammatory Response ◽  
Current Knowledge ◽  
Scar Formation ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Ecm Remodeling ◽  
Infarcted Myocardium

Myocardial Infarction (MI) initiates a series of wound healing events that begins with up-regulation of an inflammatory response and culminates in scar formation. The extracellular matrix (ECM) is intricately involved in all stages from initial break down of existing ECM to synthesis of new ECM to form the scar. This review will summarize our current knowledge on the processes involved in ECM remodeling after MI and identify the gaps that still need to be filled.

Abstract 13113: Identification of Novel Copper-dependent Wound Repair Mechanism: Role of Copper Transport Protein Antioxidant 1

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Archita Das ◽  
Gin-Fu Chen ◽  
Ha Won Kim ◽  
Sudhahar Varadarajan ◽  
Seock-Won Youn ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Wound Repair ◽  
Cell Function ◽  
Lysyl Oxidase ◽  
Mouse Skin ◽  
Impaired Wound Healing ◽  
Collagen Formation ◽  
Accelerate Wound Healing ◽  
Matrix Maturation

Copper (Cu) facilitates wound healing and angiogenesis with unknown mechanism. Bioavailability of Cu is controlled by transport-proteins, including cytosolic Cu-chaperone Atox1, which is required for activation of secretory Cu enzymes. Atox1 also functions as a Cu-dependent transcription factor, but its role in wound healing is unknown. Using mouse skin puncture model, here we show that Atox1 protein (8-fold) and Cu-level (by X-ray Fluorescence Microscopy; 2.5-fold) were increased in wounding tissue in wild type (WT) mice at day 7 when Atox1 was localized in nucleus of dermal endothelial cells (ECs) as well as cytosol of epidermal cells, granulation tissue. Furthermore, topical Cu treatment enhanced (20% vs PBS), but specific Cu chelator BCS reduced wound repair in WT mice. Importantly, Atox1 knockout (KO) mice showed abolished topical Cu-induced wound repair or impaired endogenous wound healing vs. WT mice, which was associated with decreased angiogenesis (CD31+, 45% ), proliferation (BrdU+, 60%), ROS-production (DHE+), collagen formation (Masson's Trichrome), and infiltration of macrophage (Mac3+,40%) which secrets angiogenic cytokines VEGF and SDF-1α. Mechanistically, Atox1KO mice exhibited reduced wounding-induced expression of Atox1 target proteins such as p47phox NADPH oxidase and cyclin D1 as well as extracellular matrix secretory Cu-enzyme lysyl oxidase activity. Finally, bone marrow (BM) transplantation revealed that Atox1 in both BM and tissue resident cells are required for wound repair. Consistently, Atox1 protein and Cu were markedly increased in WT-BM tissue after wounding. Impaired wound healing in Atox1 KO mice was rescued by both Atox1-gene transfer and WT-BM topical treatment in wound tissues. In summary, Atox1 senses Cu to accelerate wound healing/repair by promoting angiogenesis, inflammatory cell recruitment, proliferation, extracellular matrix maturation as well as BM cell function. Taken together, Cu-Atox1-based therapy may represent a novel therapeutic strategy to promote dermal wound healing and tissue regeneration.

scholarly journals Hyaluronan in intestinal homeostasis and inflammation: implications for fibrosis

2011 ◽  
Vol 301 (6) ◽  
pp. G945-G949 ◽  
Author(s):  
Carol A. de la Motte
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Intestinal Inflammation ◽  
Cellular Mechanisms ◽  
Matrix Component ◽  
Matrix Deposition ◽  
Fibrotic Tissue ◽  
Myofibroblast Phenotype ◽  
Extracellular Matrix Deposition ◽  
Chronic Intestinal Inflammation

The causes of fibrosis, or the inappropriate wound healing, that follows chronic intestinal inflammation are not well defined and likely involve the contributions of multiple cellular mechanisms. As other articles in this series confirm, inflammatory cytokines clearly play a role in driving cell differentiation to the myofibroblast phenotype, promoting proliferation and extracellular matrix deposition that are characteristic of fibrotic tissue. However, controlling the balance of cytokines produced and process of myofibroblast differentiation appears to be more complex. This review considers ways in which hyaluronan, an extracellular matrix component that is remodeled during the progression of colitis, may provide indirect as well as direct cues that influence the balancing act of intestinal wound healing.

Metalloproteinases and their inhibitors in angiogenesis

2003 ◽  
Vol 5 (23) ◽  
pp. 1-39 ◽  
Author(s):  
Marc A. Lafleur ◽  
Madeleine M. Handsley ◽  
Dylan R. Edwards
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Cell Function ◽  
Proteolytic Enzymes ◽  
Biologically Relevant ◽  
Physiological Processes ◽  
Adam Family ◽  
Angiogenic Inhibitors ◽  
Membrane Type

Angiogenesis, the formation of new blood vessels from the pre-existing vasculature, is an integral part of physiological processes such as embryonic development, the female reproductive cycle and wound healing. Angiogenesis is also central to a variety of pathologies including cancer, where it is recognised as being crucial for the growth of solid tumours. Matrix metalloproteinases (MMPs) are a family of soluble and membrane-anchored proteolytic enzymes that can degrade components of the extracellular matrix (ECM) as well as a growing number of modulators of cell function. Several of the MMPs, most notably MMP-2 and -9 and membrane-type-1 MMP (MT1-MMP), have been linked to angiogenesis. Potential roles for these proteases during the angiogenic process include degradation of the basement membrane and perivascular ECM components, liberation of angiogenic factors, production of endogenous angiogenic inhibitors, and the unmasking of cryptic biologically relevant sites in ECM components. This review brings together what is currently known about the functions of the MMPs and the closely related adamalysin metalloproteinase (ADAM) family in angiogenesis, and discusses how this information might be useful in manipulation of the angiogenic process, with a view to controlling aberrant neovascularisation.

Polycaprolactone nanofibers functionalized with placental derived extracellular matrix for stimulating wound healing activity

2018 ◽  
Vol 6 (42) ◽  
pp. 6767-6780 ◽  
Author(s):  
Arun Prabhu Rameshbabu ◽  
Sayanti Datta ◽  
Kamakshi Bankoti ◽  
Elavarasan Subramani ◽  
Koel Chaudhury ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Cell Migration ◽  
Growth Factors ◽  
Inflammatory Responses ◽  
Impaired Wound Healing ◽  
Wound Healing Activity

Impaired wound healing is primarily associated with inadequate angiogenesis, repressed cell migration, deficient synthesis of extracellular matrix (ECM) component/growth factors, and altered inflammatory responses in the wound bed environment.

scholarly journals Wound Healing Versus Regeneration: Role of the Tissue Environment in Regenerative Medicine

MRS Bulletin ◽  
2010 ◽  
Vol 35 (8) ◽  
pp. 597-606 ◽  
Author(s):  
Anthony Atala ◽  
Darrell J. Irvine ◽  
Marsha Moses ◽  
Sunil Shaunak
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Regenerative Medicine ◽  
Tissue Regeneration ◽  
Normal Tissue ◽  
Disease Process ◽  
Scar Formation ◽  
The Body ◽  
Mechanistic Basis

AbstractOne of the major challenges in the field of regenerative medicine is how to optimize tissue regeneration in the body by therapeutically manipulating its natural ability to form scar at the time of injury or disease. It is often the balance between tissue regeneration, a process that is activated at the onset of disease, and scar formation, which develops as a result of the disease process that determines the ability of the tissue or organ to be functional. Using biomaterials as scaffolds often can provide a “bridge” for normal tissue edges to regenerate over small distances, usually up to 1 cm. Larger tissue defect gaps typically require both scaffolds and cells for normal tissue regeneration to occur without scar formation. Various strategies can help to modulate the scar response and can potentially enhance tissue regeneration. Understanding the mechanistic basis of such multivariate interactions as the scar microenvironment, the immune system, extracellular matrix, and inflammatory cytokines may enable the design of tissue engineering and wound healing strategies that directly modulate the healing response in a manner favorable to regeneration.

scholarly journals Regeneration of Dermis: Scarring and Cells Involved

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 607 ◽  
Author(s):  
Alexandra L. Rippa ◽  
Ekaterina P. Kalabusheva ◽  
Ekaterina A. Vorotelyak
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Hair Follicle ◽  
Scar Formation ◽  
Population Characteristics ◽  
Matrix Composition ◽  
Skin Substitutes ◽  
Skin Repair ◽  
Dermal Cell

There are many studies on certain skin cell specifications and their contribution to wound healing. In this review, we provide an overview of dermal cell heterogeneity and their participation in skin repair, scar formation, and in the composition of skin substitutes. The papillary, reticular, and hair follicle associated fibroblasts differ not only topographically, but also functionally. Human skin has a number of particular characteristics that are different from murine skin. This should be taken into account in experimental procedures. Dermal cells react differently to skin wounding, remodel the extracellular matrix in their own manner, and convert to myofibroblasts to different extents. Recent studies indicate a special role of papillary fibroblasts in the favorable outcome of wound healing and epithelial-mesenchyme interactions. Neofolliculogenesis can substantially reduce scarring. The role of hair follicle mesenchyme cells in skin repair and possible therapeutic applications is discussed. Participation of dermal cell types in wound healing is described, with the addition of possible mechanisms underlying different outcomes in embryonic and adult tissues in the context of cell population characteristics and extracellular matrix composition and properties. Dermal white adipose tissue involvement in wound healing is also overviewed. Characteristics of myofibroblasts and their activity in scar formation is extensively discussed. Cellular mechanisms of scarring and possible ways for its prevention are highlighted. Data on keloid cells are provided with emphasis on their specific characteristics. We also discuss the contribution of tissue tension to the scar formation as well as the criteria and effectiveness of skin substitutes in skin reconstruction. Special attention is given to the properties of skin substitutes in terms of cell composition and the ability to prevent scarring.

Hyaluronan in skin wound healing: therapeutic applications

2020 ◽  
Vol 29 (12) ◽  
pp. 782-787
Author(s):  
Ian CC King ◽  
Parviz Sorooshian
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Clinical Practice ◽  
Inflammatory Response ◽  
Tissue Repair ◽  
Therapeutic Potential ◽  
Skin Wound ◽  
Clinical Applications ◽  
Skin Wound Healing ◽  
Proliferative Phase

Hyaluronan is a vital constituent in effective skin wound healing. This polysaccharide is ubiquitous throughout the human body and has functional significance for tissue repair and remodelling. The importance of hyaluronan in the proliferative phase of healing is diverse, impacting on cell migration, proliferation, modification of the inflammatory response and on angiogenesis. As such, it holds therapeutic potential for a variety of clinical applications that range from facilitating effective wound healing to burns management and scarring. This overview of the multifaceted roles of hyaluronan considers its current applications to clinical practice in plastic surgery as well as the latest advances in research.

scholarly journals LncRNA TRHDE-AS1 inhibit the scar fibroblasts proliferation via miR-181a-5p/PTEN axis

2021 ◽  
Author(s):  
Yanping Wei ◽  
Tingting Wang ◽  
Ningning Zhang ◽  
Yunyun Ma ◽  
Siji Shi ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Therapeutic Target ◽  
Hypertrophic Scar ◽  
Scar Formation ◽  
Invasive Growth ◽  
Skin Injury ◽  
Non Coding Rna ◽  
Direct Target ◽  
Proliferation Suppression

AbstractHypertrophic scar (HS), a fibroproliferative disorder caused by abnormal wound healing after skin injury, which is characterized by excessive deposition of extracellular matrix and invasive growth of fibroblasts. Recent studies have shown that some non-coding RNA implicated the formation of HS, but the mechanism remains unclear. In this study, we found that lncRNA TRHDE-AS1 was downregulated in HS tissues and HSFs, and the level of lncRNA TRHDE-AS1 negatively correlated with the level of miR-181a-5p in HS tissue and HSFs. Overexpressed lncRNA TRHDE-AS1 significantly suppressed miR-181a-5p level, while promoted HSFs apoptosis and inhibited HSFs proliferation. Further study shown that PTEN was a direct target of miR-181a-5p, and lncRNA TRHDE-AS1 served as a molecular sponge for miR-181a-5p to regulate the expression of PTEN. Overexpression of PTEN could eliminate lncRNA TRHDE-AS1-mediated proliferation suppression of HSFs. In conclusion, our study suggested that lncRNA TRHDE-AS1/miR-181a-5p/PTEN axis plays an important role in promoting hypertrophic scar formation, which may be effectively used as a therapeutic target for hypertrophic scar treatment.

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