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  1. Article: The molecular mechanism of hypertrophic scar.

    Zhu, Zhensen / Ding, Jie / Shankowsky, Heather A / Tredget, Edward E

    Journal of cell communication and signaling

    2013  Volume 7, Issue 4, Page(s) 239–252

    Abstract: Hypertrophic scar (HTS) is a dermal form of fibroproliferative disorder which often develops after thermal or traumatic injury to the deep regions of the skin and is characterized by excessive deposition and alterations in morphology of collagen and ... ...

    Abstract Hypertrophic scar (HTS) is a dermal form of fibroproliferative disorder which often develops after thermal or traumatic injury to the deep regions of the skin and is characterized by excessive deposition and alterations in morphology of collagen and other extracellular matrix (ECM) proteins. HTS are cosmetically disfiguring and can cause functional problems that often recur despite surgical attempts to remove or improve the scars. In this review, the roles of various fibrotic and anti-fibrotic molecules are discussed in order to improve our understanding of the molecular mechanism of the pathogenesis of HTS. These molecules include growth factors, cytokines, ECM molecules, and proteolytic enzymes. By exploring the mechanisms of this form of dermal fibrosis, we seek to provide some insight into this form of dermal fibrosis that may allow clinicians to improve treatment and prevention in the future.
    Language English
    Publishing date 2013-03-18
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2299380-0
    ISSN 1873-961X ; 1873-9601
    ISSN (online) 1873-961X
    ISSN 1873-9601
    DOI 10.1007/s12079-013-0195-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A novel subpopulation of peripheral blood mononuclear cells presents in major burn patients.

    Liu, Hongbin / Ding, Jie / Ma, Zengshuan / Zhu, Zhenshen / Shankowsky, Heather A / Tredget, Edward E

    Burns : journal of the International Society for Burn Injuries

    2015  Volume 41, Issue 5, Page(s) 998–1007

    Abstract: Hypertrophic scars (HTS) are generally believed to result from proliferation and activation of resident connective tissue fibroblasts after burns. To demonstrate a potential role of blood-borne cells, the peripheral blood mononuclear cells (PBMCs) and ... ...

    Abstract Hypertrophic scars (HTS) are generally believed to result from proliferation and activation of resident connective tissue fibroblasts after burns. To demonstrate a potential role of blood-borne cells, the peripheral blood mononuclear cells (PBMCs) and the effect of PBMCs on dermal fibroblast behavior was investigated. Flow cytometry was used to analyze the surface and intracellular protein expression of PBMCs and fibroblasts. Transwell migration assay, enzyme-linked immunosorbent assay and real-time reverse transcription polymerase chain reaction was performed to assess fibroblast functions. We identified a novel subpopulation of PBMCs in burn patients in vivo that appears at an early stage following major thermal injuries, which primarily express procollagen 1, leukocyte specific protein 1, CD204, toll-like receptor 4 and stromal cell-derived factor 1 (SDF-1) receptor CXCR4. In vitro, the conditioned media from burn patient PBMCs up-regulated the expression of fibrotic growth factors and extracellular matrix molecules, down-regulated antifibrotic factor decorin, enhanced cell chemotaxis and promoted cell differentiation into contractile myofibroblasts in dermal fibroblasts. After thermal injury, this novel subpopulation of PBMCs is systemically triggered and attracted to the wounds under SDF-1/CXCR4 signaling where they appear to modulate the functions of resident connective tissue cells and thus contribute to the development of HTS.
    MeSH term(s) Adult ; Body Surface Area ; Burns/blood ; Burns/pathology ; Cell Differentiation ; Cell Migration Assays ; Cells, Cultured ; Chemotaxis ; Cicatrix, Hypertrophic/blood ; Connective Tissue Cells/cytology ; Connective Tissue Cells/metabolism ; Decorin/metabolism ; Down-Regulation ; Enzyme-Linked Immunosorbent Assay ; Extracellular Matrix Proteins/metabolism ; Female ; Fibroblasts/cytology ; Humans ; In Vitro Techniques ; Leukocytes, Mononuclear/cytology ; Leukocytes, Mononuclear/metabolism ; Macrophages/cytology ; Macrophages/metabolism ; Male ; Microfilament Proteins/metabolism ; Middle Aged ; Myofibroblasts/cytology ; Procollagen/metabolism ; Receptors, CXCR4/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Scavenger Receptors, Class A/metabolism ; Signal Transduction ; Skin/cytology ; Toll-Like Receptor 4/metabolism ; Trauma Severity Indices ; Young Adult
    Chemical Substances CXCR4 protein, human ; DCN protein, human ; Decorin ; Extracellular Matrix Proteins ; LSP1 protein, human ; MSR1 protein, human ; Microfilament Proteins ; Procollagen ; Receptors, CXCR4 ; Scavenger Receptors, Class A ; TLR4 protein, human ; Toll-Like Receptor 4
    Language English
    Publishing date 2015-08
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 197308-3
    ISSN 1879-1409 ; 0305-4179
    ISSN (online) 1879-1409
    ISSN 0305-4179
    DOI 10.1016/j.burns.2014.12.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Synergistic effect of vitamin D and low concentration of transforming growth factor beta 1, a potential role in dermal wound healing.

    Ding, Jie / Kwan, Peter / Ma, Zengshuan / Iwashina, Takashi / Wang, Jianfei / Shankowsky, Heather A / Tredget, Edward E

    Burns : journal of the International Society for Burn Injuries

    2016  Volume 42, Issue 6, Page(s) 1277–1286

    Abstract: Dermal wound healing, in which transforming growth factor beta 1 (TGFβ1) plays an important role, is a complex process. Previous studies suggest that vitamin D has a potential regulatory role in TGFβ1 induced activation in bone formation, and there is ... ...

    Abstract Dermal wound healing, in which transforming growth factor beta 1 (TGFβ1) plays an important role, is a complex process. Previous studies suggest that vitamin D has a potential regulatory role in TGFβ1 induced activation in bone formation, and there is cross-talk between their signaling pathways, but research on their effects in other types of wound healing is limited. The authors therefore wanted to explore the role of vitamin D and its interaction with low concentration of TGFβ1 in dermal fibroblast-mediated wound healing through an in vitro study. Human dermal fibroblasts were treated with vitamin D, TGFβ1, both, or vehicle, and then the wound healing functions of dermal fibroblasts were measured. To further explore possible mechanisms explaining the synergistic effect of vitamin D and TGFβ1, targeted gene silencing of the vitamin D receptor was performed. Compared to either factor alone, treatment of fibroblasts with both vitamin D and low concentration of TGFβ1 increased gene expression of TGFβ1, connective tissue growth factor, and fibronectin 1, and enhanced fibroblast migration, myofibroblast formation, and collagen production. Vitamin D receptor gene silencing blocked this synergistic effect of vitamin D and TGFβ1 on both collagen production and myofibroblast differentiation. Thus a synergistic effect of vitamin D and low TGFβ1 concentration was found in dermal fibroblast-mediated wound healing in vitro. This study suggests that supplementation of vitamin D may be an important step to improve wound healing and regeneration in patients with a vitamin D deficiency.
    MeSH term(s) Adult ; Calcitriol/pharmacology ; Cell Differentiation/drug effects ; Cell Movement/drug effects ; Cells, Cultured ; Chromatography, Liquid ; Connective Tissue Growth Factor/drug effects ; Connective Tissue Growth Factor/genetics ; Dermis/drug effects ; Dermis/metabolism ; Drug Synergism ; Female ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Fibronectins/drug effects ; Fibronectins/genetics ; Humans ; Hydroxyproline/metabolism ; In Vitro Techniques ; Mass Spectrometry ; Myofibroblasts/drug effects ; Real-Time Polymerase Chain Reaction ; Receptors, Calcitriol/drug effects ; Receptors, Calcitriol/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Smad2 Protein/drug effects ; Smad2 Protein/genetics ; Smad3 Protein/drug effects ; Smad3 Protein/genetics ; Smad7 Protein/drug effects ; Smad7 Protein/genetics ; Transforming Growth Factor beta1/drug effects ; Transforming Growth Factor beta1/genetics ; Transforming Growth Factor beta1/pharmacology ; Vitamins/pharmacology ; Wound Healing/drug effects
    Chemical Substances FN1 protein, human ; Fibronectins ; Receptors, Calcitriol ; SMAD2 protein, human ; SMAD3 protein, human ; SMAD7 protein, human ; Smad2 Protein ; Smad3 Protein ; Smad7 Protein ; TGFB1 protein, human ; Transforming Growth Factor beta1 ; VDR protein, human ; Vitamins ; Connective Tissue Growth Factor (139568-91-5) ; Calcitriol (FXC9231JVH) ; Hydroxyproline (RMB44WO89X)
    Language English
    Publishing date 2016-09
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 197308-3
    ISSN 1879-1409 ; 0305-4179
    ISSN (online) 1879-1409
    ISSN 0305-4179
    DOI 10.1016/j.burns.2016.03.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Deep dermal fibroblast profibrotic characteristics are enhanced by bone marrow-derived mesenchymal stem cells.

    Ding, Jie / Ma, Zengshuan / Shankowsky, Heather A / Medina, Abelardo / Tredget, Edward E

    Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society

    2013  Volume 21, Issue 3, Page(s) 448–455

    Abstract: Hypertrophic scars are a significant fibroproliferative disorder complicating deep injuries to the skin. We hypothesize that activated deep dermal fibroblasts are subject to regulation by bone marrow-derived mesenchymal stem cells (BM-MSCs), which leads ... ...

    Abstract Hypertrophic scars are a significant fibroproliferative disorder complicating deep injuries to the skin. We hypothesize that activated deep dermal fibroblasts are subject to regulation by bone marrow-derived mesenchymal stem cells (BM-MSCs), which leads to the development of excessive fibrosis following deep dermal injury. We found that the expression of fibrotic factors was higher in deep burn wounds compared with superficial burn wounds collected from burn patients with varying depth of skin injury. We characterized deep and superficial dermal fibroblasts, which were cultured from the deep and superficial dermal layers of normal uninjured skin obtained from abdominoplasty patients, and examined the paracrine effects of BM-MSCs on the fibrotic activities of the cells. In vitro, deep dermal fibroblasts were found higher in the messenger RNA (mRNA) levels of type 1 collagen, alpha smooth muscle actin, transforming growth factor beta, stromal cell-derived factor 1, and tissue inhibitor of metalloproteinase 1, an inhibitor of collagenase (matrix metalloproteinase 1). As well, deep dermal fibroblasts had low matrix metalloproteinase 1 mRNA, produced more collagen, and contracted collagen lattices significantly greater than superficial fibroblasts. By co-culturing layered fibroblasts with BM-MSCs in a transwell insert system, BM-MSCs enhanced the fibrotic behavior of deep dermal fibroblasts, which suggests a possible involvement of BM-MSCs in the pathogenesis of hypertrophic scarring.
    MeSH term(s) Adult ; Burns/metabolism ; Burns/pathology ; Burns/surgery ; Cell Proliferation ; Cells, Cultured ; Cicatrix, Hypertrophic/metabolism ; Cicatrix, Hypertrophic/pathology ; Cicatrix, Hypertrophic/prevention & control ; Collagen/biosynthesis ; Collagen/genetics ; Female ; Fibroblasts/metabolism ; Fibroblasts/pathology ; Gene Expression Regulation ; Humans ; Laser-Doppler Flowmetry ; Male ; Mesenchymal Stromal Cells ; Middle Aged ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Skin/metabolism ; Skin/pathology ; Stem Cell Transplantation/methods ; Wound Healing/physiology
    Chemical Substances RNA, Messenger ; Collagen (9007-34-5)
    Language English
    Publishing date 2013-05
    Publishing country United States
    Document type Clinical Trial ; Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1174873-4
    ISSN 1524-475X ; 1067-1927
    ISSN (online) 1524-475X
    ISSN 1067-1927
    DOI 10.1111/wrr.12046
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Reduced decorin, fibromodulin, and transforming growth factor-β3 in deep dermis leads to hypertrophic scarring.

    Honardoust, Dariush / Varkey, Mathew / Marcoux, Yvonne / Shankowsky, Heather A / Tredget, Edward E

    Journal of burn care & research : official publication of the American Burn Association

    2012  Volume 33, Issue 2, Page(s) 218–227

    Abstract: Hypertrophic scar (HTS) occurs after injuries involving the deep dermis, while superficial wounds (SWs) to the skin heal with minimal or no scarring. The levels of transforming growth factor (TGF)-β1 and small leucine-rich proteoglycans (SLRPs) with ... ...

    Abstract Hypertrophic scar (HTS) occurs after injuries involving the deep dermis, while superficial wounds (SWs) to the skin heal with minimal or no scarring. The levels of transforming growth factor (TGF)-β1 and small leucine-rich proteoglycans (SLRPs) with fibroblast subtype and function may influence the development of HTS. The aim of this study was to characterize the expression and localization of factors that regulate wound healing including SLRPs, TGF-β1, and TGF-β3 in an experimental human SW and deep wound (DW) scar model including fibroblasts from superficial and deep layers of normal dermis. A 6-cm horizontal dermal scratch experimental wound was created, which consisted of progressively deeper wounds that were superficial at one end (0-0.75 mm deep) and deep (0.75-3 mm deep) at the other end, located on the anterior thigh of an adult male. Immunofluorescence staining, immunoblotting, reverse transcription polymerase chain reaction, and flow cytometry were performed to analyze the cellular and molecular differences between the SW scar and DW scar as well as fibroblasts isolated from superficial layer (L1) and deep layer (L5) of normal dermis. Comparing SWs and L1 fibroblasts, the expression of decorin, fibromodulin, and TGF-β3 was considerably lower than in DWs and L5 fibroblasts; however, TGF-β1 was higher in the deeper dermal wounds. When compared with L1 fibroblasts, L5 fibroblasts had lower Thy-1 immunoreactivity and significantly higher expression of TGF-β receptor type II. Decreased antifibrotic molecules in matrix of deep dermis of the skin and the unique features of the associated fibroblasts including an increased sensitivity to TGF-β1 stimulation contribute to the development of HTS after injuries involving the deep dermis.
    MeSH term(s) Analysis of Variance ; Blotting, Western ; Burns/complications ; Burns/metabolism ; Burns/therapy ; Cicatrix, Hypertrophic/etiology ; Cicatrix, Hypertrophic/metabolism ; Decorin/metabolism ; Down-Regulation ; Extracellular Matrix Proteins/metabolism ; Fibroblasts/metabolism ; Fibromodulin ; Flow Cytometry ; Fluorescent Antibody Technique ; Humans ; Male ; Microscopy, Confocal ; Occlusive Dressings ; Polymerase Chain Reaction ; Proteoglycans/metabolism ; Thigh ; Transforming Growth Factor beta3/metabolism
    Chemical Substances Decorin ; Extracellular Matrix Proteins ; FMOD protein, human ; Proteoglycans ; TGFB3 protein, human ; Transforming Growth Factor beta3 ; Fibromodulin (126468-95-9)
    Language English
    Publishing date 2012-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2224246-6
    ISSN 1559-0488 ; 1559-047X
    ISSN (online) 1559-0488
    ISSN 1559-047X
    DOI 10.1097/BCR.0b013e3182335980
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Deep dermal fibroblasts refractory to migration and decorin-induced apoptosis contribute to hypertrophic scarring.

    Honardoust, Dariush / Ding, Jie / Varkey, Mathew / Shankowsky, Heather A / Tredget, Edward E

    Journal of burn care & research : official publication of the American Burn Association

    2012  Volume 33, Issue 5, Page(s) 668–677

    Abstract: Hypertrophic scar (HTS) represents the dermal equivalent of fibroproliferative disorders. Fibroblasts from the deep dermis are implicated in the development of HTS after injuries that involve deeper areas of the skin. However, fibroblasts that reside in ... ...

    Abstract Hypertrophic scar (HTS) represents the dermal equivalent of fibroproliferative disorders. Fibroblasts from the deep dermis are implicated in the development of HTS after injuries that involve deeper areas of the skin. However, fibroblasts that reside in the superficial layer of the skin show antifibrotic properties, and injuries limited to this area heal with little or no scarring. Previously, cellular and molecular characteristics of superficial fibroblasts and deep dermal fibroblasts that may influence HTS formation were analyzed. In this study, differences in cellular behavior between superficial fibroblasts and deep dermal fibroblasts that may also affect the development of HTS or tissue fibrosis were further characterized. Immunostaining and migration, adhesion, apoptosis, and cell viability assays were performed in fibroblasts from the superficial and deep dermis. Reverse-transcription polymerase chain reaction was used to examine the gene expression of molecules involved in cell death after treatment of fibroblasts with decorin. When compared with superficial fibroblasts, deep dermal fibroblasts showed lower migration rates. Although all the fibroblasts tested showed no difference in adhesion to fibronectin, superficial fibroblasts demonstrated increased apoptotic and dead cells when treated with decorin. Decorin resulted in a significant increase in the expression of apoptosis markers, histone-1, caspase-1, caspase-8, and p53 in superficial fibroblasts when compared with deep dermal fibroblasts. Taken together, the findings suggest that reduced migration, lack of decorin, and resistance of deep dermal fibroblasts to decorin-induced apoptosis may result in hypercellularity in injuries involving the deep dermis, leading to deposition of excess extracellular matrix and HTS formation.
    MeSH term(s) Apoptosis ; Caspase 8 ; Cell Adhesion ; Cell Migration Assays ; Cicatrix, Hypertrophic/pathology ; Decorin ; Extracellular Matrix ; Extracellular Matrix Proteins ; Fibroblasts ; Humans ; Proteoglycans ; RNA, Messenger ; Signal Transduction ; Wound Healing
    Chemical Substances Decorin ; Extracellular Matrix Proteins ; Proteoglycans ; RNA, Messenger ; Caspase 8 (EC 3.4.22.-)
    Language English
    Publishing date 2012-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2224246-6
    ISSN 1559-0488 ; 1559-047X
    ISSN (online) 1559-0488
    ISSN 1559-047X
    DOI 10.1097/BCR.0b013e31824088e3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The therapeutic potential of a C-X-C chemokine receptor type 4 (CXCR-4) antagonist on hypertrophic scarring in vivo.

    Ding, Jie / Ma, Zengshuan / Liu, Hongbin / Kwan, Peter / Iwashina, Takashi / Shankowsky, Heather A / Wong, Donald / Tredget, Edward E

    Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society

    2014  Volume 22, Issue 5, Page(s) 622–630

    Abstract: Effective prevention and treatment of hypertrophic scars (HTSs), a dermal form of fibrosis that frequently occurs following thermal injury to deep dermis, are unsolved significant clinical problems. Previously, we have found that stromal cell-derived ... ...

    Abstract Effective prevention and treatment of hypertrophic scars (HTSs), a dermal form of fibrosis that frequently occurs following thermal injury to deep dermis, are unsolved significant clinical problems. Previously, we have found that stromal cell-derived factor 1/CXCR4 signaling is up-regulated during wound healing in burn patients and HTS tissue after thermal injury. We hypothesize that blood-borne mononuclear cells are recruited into wound sites after burn injury through the chemokine pathway of stromal cell-derived factor 1 and its receptor CXCR4. Deep dermal injuries to the skin are often accompanied by prolonged inflammation, which leads to chemotaxis of mononuclear cells into the wounds by chemokine signaling where fibroblast activation occurs and ultimately HTS are formed. Blocking mononuclear cell recruitment and fibroblast activation, CXCR4 antagonism is expected to reduce or minimize scar formation. In this study, the inhibitory effect of CXCR4 antagonist CTCE-9908 on dermal fibrosis was determined in vivo using a human HTS-like nude mouse model, in which split-thickness human skin is transplanted into full-thickness dorsal excisional wounds in athymic mice, where these wounds subsequently develop fibrotic scars that resemble human HTS as previously described. CTCE-9908 significantly attenuated scar formation and contraction, reduced the accumulation of macrophages and myofibroblasts, enhanced the remodeling of collagen fibers, and down-regulated the gene and protein expression of fibrotic growth factors in the human skin tissues. These findings support the potential therapeutic value of CXCR4 antagonist in dermal fibrosis and possibly other fibroproliferative disorders.
    MeSH term(s) Adult ; Animals ; Cicatrix, Hypertrophic/pathology ; Cicatrix, Hypertrophic/prevention & control ; Dermis/drug effects ; Dermis/pathology ; Disease Models, Animal ; Female ; Fibrosis ; Humans ; Male ; Mice, Nude ; Middle Aged ; Peptides/pharmacology ; Receptors, CXCR4/antagonists & inhibitors ; Skin Transplantation ; Wound Healing/drug effects
    Chemical Substances CTCE-9908 ; Peptides ; Receptors, CXCR4
    Keywords covid19
    Language English
    Publishing date 2014-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1174873-4
    ISSN 1524-475X ; 1067-1927
    ISSN (online) 1524-475X
    ISSN 1067-1927
    DOI 10.1111/wrr.12208
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Small leucine-rich proteoglycans, decorin and fibromodulin, are reduced in postburn hypertrophic scar.

    Honardoust, Dariush / Varkey, Mathew / Hori, Keijiro / Ding, Jie / Shankowsky, Heather A / Tredget, Edward E

    Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society

    2011  Volume 19, Issue 3, Page(s) 368–378

    Abstract: Small leucine-rich proteoglycans (SLRPs) are extracellular matrix molecules that regulate collagen fibrillogenesis and inhibit transforming growth factor-β activity; thus, they may play a critical role in wound healing and scar formation. Hypertrophic ... ...

    Abstract Small leucine-rich proteoglycans (SLRPs) are extracellular matrix molecules that regulate collagen fibrillogenesis and inhibit transforming growth factor-β activity; thus, they may play a critical role in wound healing and scar formation. Hypertrophic scarring is a dermal form of fibroproliferative disorders, which occurs in over 70% of burn patients and leads to disfigurement and limitations in function. By understanding the cellular and molecular mechanisms that lead to scarring after injury, new clinical therapeutic approaches can by developed to minimize abnormal scar formation in hypertrophic scarring and other fibroproliferative disorders. To study the expression and localization of SLRPs with connective tissue cells in tissue immunohistochemistry, immunofluorescence staining, immunoblotting, and reverse-transcription polymerase chain reaction were used in normal skin and hypertrophic scar (HTS). In normal skin, there was more decorin and fibromodulin accumulation in the superficial layers than in the deeper dermal layers. The levels of decorin and fibromodulin were significantly lower in HTS, whereas biglycan was increased when compared with normal skin. There was an increased expression of biglycan, fibromodulin, and lumican in the basement membrane and around basal epithelial cells. In contrast, these proteoglycans were absent or weakly expressed in HTS. The findings suggest that down-regulation of SLRPs after wound healing in deep injuries to the skin plays an important role in the development of fibrosis and HTS.
    MeSH term(s) Adult ; Biglycan/metabolism ; Blotting, Western ; Burns/complications ; Burns/metabolism ; Child ; Cicatrix, Hypertrophic/etiology ; Cicatrix, Hypertrophic/metabolism ; Decorin/metabolism ; Down-Regulation/physiology ; Extracellular Matrix Proteins/metabolism ; Female ; Fibroblasts/physiology ; Fibromodulin ; Fluorescent Antibody Technique ; Humans ; Male ; Microscopy, Confocal ; Middle Aged ; Proteoglycans/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Wound Healing/physiology
    Chemical Substances Biglycan ; Decorin ; Extracellular Matrix Proteins ; FMOD protein, human ; Proteoglycans ; Fibromodulin (126468-95-9)
    Language English
    Publishing date 2011-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1174873-4
    ISSN 1524-475X ; 1067-1927
    ISSN (online) 1524-475X
    ISSN 1067-1927
    DOI 10.1111/j.1524-475X.2011.00677.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: The use of laser Doppler imaging as a predictor of burn depth and hypertrophic scar postburn injury.

    Stewart, Tara Lynn / Ball, Brandon / Schembri, Paul J / Hori, Keijiro / Ding, Jie / Shankowsky, Heather A / Tredget, Edward E

    Journal of burn care & research : official publication of the American Burn Association

    2012  Volume 33, Issue 6, Page(s) 764–771

    Abstract: Hypertrophic scarring (HTS) is a fibroproliferative disorder that commonly develops after severe burn injuries. Overexpression of transforming growth factor-β (TGF-β) by an increased number of fibrocytes has been associated with increased extracellular ... ...

    Abstract Hypertrophic scarring (HTS) is a fibroproliferative disorder that commonly develops after severe burn injuries. Overexpression of transforming growth factor-β (TGF-β) by an increased number of fibrocytes has been associated with increased extracellular matrix molecule expression leading to HTS. The most widely accepted adjuvant to clinical assessment of burn depth is laser Doppler imaging (LDI) and may predict injury to the dermis that corresponds to cellular and molecular changes associated with HTS. A prospective, blinded, control trial was performed comparing LDI and clinical assessment for the decision to operate. Immunohistochemistry and real-time reverse transcription polymerase chain reaction was performed to determine whether there is a correlation between histological assessment of burn depth and LDI, and the presence of fibrocytes was detected using confocal microscopy. The positive predictive value for a burn requiring a graft was calculated to be >90%. Immunohistochemistry on biopsy samples revealed an increased expression of TGF-β, connective tissue growth factor, heat shock protein 47, and collagen type I in deep burn wounds compared to superficial burns. Using the fibrocyte-specific markers procollagen type I and lymphocyte-specific protein-1, there was an increased number of fibrocytes in deep burn areas compared to superficial burn. In deep burn injuries, increased infiltration of fibrocytes occurs leading to an overexpression of TGF-β1 and connective tissue growth factor. More importantly, LDI was >90% accurate at predicting the need for excision and grafting. The accuracy of the decision to debride deep dermal burns to avoid HTS using both clinical parameters and LDI was supported by histological and biochemical measurements.
    MeSH term(s) Adolescent ; Adult ; Aged ; Biopsy ; Burns/metabolism ; Burns/pathology ; Child ; Child, Preschool ; Cicatrix, Hypertrophic/metabolism ; Cicatrix, Hypertrophic/pathology ; Collagen Type I/metabolism ; Connective Tissue Growth Factor/metabolism ; Female ; HSP47 Heat-Shock Proteins/metabolism ; Humans ; Immunohistochemistry ; Infant ; Laser-Doppler Flowmetry/methods ; Male ; Microfilament Proteins/metabolism ; Microscopy, Confocal ; Middle Aged ; Predictive Value of Tests ; Prospective Studies ; Real-Time Polymerase Chain Reaction ; Transforming Growth Factor beta/metabolism
    Chemical Substances Collagen Type I ; HSP47 Heat-Shock Proteins ; LSP1 protein, human ; Microfilament Proteins ; Transforming Growth Factor beta ; Connective Tissue Growth Factor (139568-91-5)
    Language English
    Publishing date 2012-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2224246-6
    ISSN 1559-0488 ; 1559-047X
    ISSN (online) 1559-0488
    ISSN 1559-047X
    DOI 10.1097/BCR.0b013e318257db36
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: A survey of invasive catheter practices in U.S. burn centers.

    Sheridan, Robert L / Neely, Alice N / Castillo, Mayra A / Shankowsky, Heather A / Fagan, Shawn P / Chung, Kevin K / Weber, Joan M

    Journal of burn care & research : official publication of the American Burn Association

    2012  Volume 33, Issue 6, Page(s) 741–746

    Abstract: Burn-specific guidelines for optimal catheter rotation, catheter type, insertion methods, and catheter site care do not exist, and practices vary widely from one burn unit to another. The purpose of this study was to define current practices and identify ...

    Abstract Burn-specific guidelines for optimal catheter rotation, catheter type, insertion methods, and catheter site care do not exist, and practices vary widely from one burn unit to another. The purpose of this study was to define current practices and identify areas of practice variation for future clinical investigation. An online survey was sent to the directors of 123 U.S. burn centers. The survey consisted of 23 questions related to specific practices in placement and maintenance of central venous catheters (CVCs), arterial catheters, and peripherally inserted central catheters (PICCs). The overall response rate was 36%; response rate from verified centers was 52%. Geographic representation was wide. CVC and arterial catheter replacement varied from every 3 days (24% of sites) to only for overt infection (24% of sites); 23% of sites did not use the femoral position for CVC placement. Nearly 60% of units used some kind of antiseptic catheter. Physicians inserted the majority of catheters, and 22% of sites used nonphysicians for at least some insertions. Ultrasound was routinely used by less than 50% of units. A wide variety of post-insertion dressing protocols were followed. PICCs were used in some critically injured patients in 37% of units; the majority of these users did not rotate PICCs. Thus, it can be surmised that wide practice variation exists among burn centers with regard to insertion and maintenance of invasive catheters. Areas with particular variability that would be appropriate targets of clinical investigation are line rotation protocols, catheter site care protocols, and use of PICCs in acute burns.
    MeSH term(s) Burn Units ; Catheterization/standards ; Catheterization/statistics & numerical data ; Humans ; Practice Patterns, Physicians'/statistics & numerical data ; Surveys and Questionnaires ; United States
    Language English
    Publishing date 2012-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2224246-6
    ISSN 1559-0488 ; 1559-047X
    ISSN (online) 1559-0488
    ISSN 1559-047X
    DOI 10.1097/BCR.0b013e318254d4ab
    Database MEDical Literature Analysis and Retrieval System OnLINE

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