Histamine and collagen synthesis in keloid and hypertrophic scar

Cohen, I. Kelman; Beaven, Michael A.; Hořáková, Zuzana; Keiser, Harry R.

doi:10.1097/00006534-197306000-00062

Cited by 15 publications

(18 citation statements)

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“…Several studies in the past have shown a larger number of mast cells in fibrotic lung disorders 24, sclerodermatous skin lesions 25, and hypertrophic scar tissue 26–28. The cytoplasmic granules of mast cells contain several factors: some cause vasodilatation, whereas others can stimulate dermal matrix production 14, 29–32. However, in this and other studies 33, no differences in mast cell numbers were found between hypertrophic and normal scars.…”

Section: Discussionmentioning

confidence: 48%

Hypertrophic scar formation is associated with an increased number of epidermal Langerhans cells

Niessen

Schalkwijk

Vos

et al. 2003

The Journal of Pathology

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The exact pathogenesis of hypertrophic scar and keloid formation is still unknown and a good therapy to prevent or treat these scars is lacking. Because immunological processes seem to be important in excessive scar formation, immunological cells and parameters were studied in a standardized breast reduction wound-healing model in the present study. Standardized scar samples were taken from infra-mammary breast reduction scars, 3 and 12 months following surgery. The samples were investigated for their number of mast cells, Langerhans cells, T-lymphocytes, and macrophages, and the presence of interleukin-4 (IL-4) and counter-regulating interferon-gamma (gamma-IFN), in relation to the scar's clinical appearance--normal or hypertrophic. In this study, hypertrophic scar formation was significantly associated with an increased number of epidermal Langerhans cells (p=0.0001) and significantly (p<0.05) increased expression of epidermal IL-4. No relationship was found between mast cell, T-lymphocyte and macrophage numbers or gamma-IFN staining and the formation of normal or hypertrophic scars. These results, combined with previous observation of abnormal keratinocyte behaviour in this context, indicate that the epidermal immune barrier plays an important role in the development of hypertrophic scars.

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Section: Discussionmentioning

confidence: 48%

Hypertrophic scar formation is associated with an increased number of epidermal Langerhans cells

Niessen

Schalkwijk

Vos

et al. 2003

The Journal of Pathology

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“…27,28 The strong association of mast cells with fibrosis has been well established in several conditions, including KD. 29 EGCG can attenuate mast cell-induced collagen production and fibroblast proliferation in keloid in vitro, coculture models through STAT3 and PI-3K pathways. 10 That EGCG almost depleted mast cell numbers in the current keloid OC model confirms the potent impact of EGCG on mast cells and raises the possibility that the EGCG-induced reduction of intrakeloid collagen production may have occurred at least, in part, via downregulation of STAT3 and PI-3K.…”

Section: Discussionmentioning

confidence: 93%

Ex vivo evaluation of antifibrotic compounds in skin scarring: EGCG and silencing of PAI-1 independently inhibit growth and induce keloid shrinkage

Syed

Bagabir

Paus

et al. 2013

Laboratory Investigation

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Keloid disease (KD) is a common fibroproliferative disorder of unknown etiopathogenesis. Its unique occurrence in human skin and lack of animal models pose challenges for KD research. The lack of a suitable model in KD and overreliance on cell culture has hampered the progress in developing new treatments. Therefore, we evaluated the effect of two promising candidate antifibrotic therapies: ( À )-epigallocatechin-3-gallate (EGCG) and plasminogen activator inhibitor-1 (PAI-1) silencing in a long-term human keloid organ culture (OC). Four millimeters of air-liquid interface (ALI) keloid explants on collagen gel matrix in serum-free medium (n ¼ 8 cases) were treated with different modalities (EGCG treatment; PAI-1 knockdown by short interfering RNA (siRNA) and application of dexamethasone (DEX) as control). Normal skin (n ¼ 6) was used as control (only for D0 keloid-untreated comparison). Besides routine histology and quantitative (immuno-) histomorphometry, the key phenotypic and growth parameters of KD were assessed. Results demonstrated that EGCG reduced keloid volume significantly (40% by week 4), increased apoptosis (Z40% from weeks 1 to 4), and decreased proliferation (r17% in week 2). EGCG induced epidermal shrinkage, reduced collagen-I and -III at mRNA and protein levels, depleted 98% of keloid-associated mast cells, and reduced the percentage of both cellularity and blood vessel count by week 4. Knockdown of PAI-1 significantly reduced keloid volume by 28% in week 4, respectively, and reduced collagen-I and -III at both mRNA and protein levels. As expected, DEX increased keloid apoptosis, decreased keloid proliferation, and collagen synthesis, but induced connective tissue growth factor overexpression. In conclusion, using keloid OC model, we provide the first functional evidence for testing candidate antifibrotic compounds in KD. We show that EGCG and PAI-1 silencing effectively inhibits growth and induces shrinkage of human keloid tissue in situ. Therefore, the application of EGCG, PAI-1 silencing, and other emerging compounds tested using this model may provide effective treatment and potentially aid in the prevention of recurrence of KD following surgery. Keloid disease (KD) is a benign hyperproliferative dermal disease of unknown etiopathogenesis with ill-defined treatment, 1 which is unique to humans. 2 KD can arise following an abnormal wound healing process in genetically susceptible individuals. 2 The hallmark of KD is excessive deposition of extracellular matrix (ECM) in the dermis. 3 The lack of an animal model that can truly mimic human KD in vivo condition imposes limitations when investigating functional activities of potential therapeutic agents in treating KD. 4,5 However, these models have failed to provide the essential components of skin tissue that occur in vivo, such as mature ECM, blood vessels, inflammatory cells, and intrinsic and extrinsic biochemical interactions. Therefore, the ultimate aim of this study was to determine the applicability of recent research findings in existing i...

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“…Clarification of the different lesional sites and degree of maturation of keloid scars may also be of particular importance to understanding the disease mechanism, as it is possible that they are at different stages of wound healing. Further research into the cellular and molecular mechanisms involved in the abnormal wound healing of keloids, may be important for devising improved strategies in clinical management of keloid disease 157 …”

Section: Discussionmentioning

confidence: 99%

Molecular dissection of abnormal wound healing processes resulting in keloid disease

Shih

Garside

McGrouther

et al. 2010

Wound Repair and Regeneration

207

208

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Keloids are locally aggressive scars that typically invade into healthy surrounding skin and cause both physical and psychosocial distress to the patient. These pathological scars occur following minimal skin trauma after a variety of causes including burns and trauma. Although the pathogenesis of keloid disease is not well understood, it is considered to be the end product of an abnormal healing process. The aim of this review was to investigate the molecular and cellular pathobiology of keloid disease in relation to the normal wound healing process. The molecular aberrances in keloids that correlate with the molecular mechanisms in normal wound healing can be categorized into three groups: (1) extracellular matrix proteins and their degradation, (2) cytokines and growth factors, and (3) apoptotic pathways. With respect to cellular involvements, fibroblasts are the most well-studied cell population. However, it is unclear whether the fibroblast is the causative cell; they are modulated by other cell populations in wound repair, such as keratinocytes and macrophages. This review presents a detailed account of individual phases of the healing process and how they may potentially be implicated in aberrant raised scar formation, which may help in clarifying the mechanisms involved in keloid disease pathogenesis.

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Histamine and collagen synthesis in keloid and hypertrophic scar

Cited by 15 publications

References 0 publications

Hypertrophic scar formation is associated with an increased number of epidermal Langerhans cells

Hypertrophic scar formation is associated with an increased number of epidermal Langerhans cells

Ex vivo evaluation of antifibrotic compounds in skin scarring: EGCG and silencing of PAI-1 independently inhibit growth and induce keloid shrinkage

Molecular dissection of abnormal wound healing processes resulting in keloid disease

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