Skin mast cell promotion of matrix remodeling in burn wound healing in mice: relevance of chymase

Nishikori, Yoriko; Kakizoe, Eiichi; Kobayashi, Yuta; Shimoura, Keiko; Okunishi, Hideki; Dekio, Satoshi

doi:10.1007/s004030050351

Cited by 70 publications

(57 citation statements)

References 33 publications

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“…Mast cells play important roles in multiple physiological and pathological processes, including anaphylaxis and allergic inflammation (2,3), host defense against bacterial (4) and parasitic infection (5), control of endothelin-mediated toxicity (6), regulation of angiogenesis (7), and remodeling of the extracellular matrix (8). Several pathological conditions are associated with accumulation and activation of mast cells in specific organs and tissues, such as bronchi of asthmatic patients (9,10), synovial fluids of patients with rheumatic diseases (11), and certain types of solid tumors in cancer patients (12,13).…”

Section: Ast Cells Are Hemopoietic Cells That Reside In a Varietymentioning

confidence: 99%

HIF-1α Is Up-Regulated in Activated Mast Cells by a Process That Involves Calcineurin and NFAT

Walczak‐Drzewiecka

Ratajewski

Wagner

et al. 2008

The Journal of Immunology

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Mast cells play important roles in many pathological conditions where local hypoxia is observed, including asthma, rheumatic diseases, and certain types of cancer. Here, we investigated how expression of the hypoxia-inducible factor 1, α subunit gene (HIF1A), is regulated in mast cells. The product of HIF1A is hypoxia-inducible factor 1α (HIF-1α), is a major nuclear transcription factor modulating gene expression in response to hypoxic conditions. We observed that under hypoxic conditions, exposure of mast cells to ionomycin and substance P resulted in significant up-regulation of HIF1A expression as compared with resting mast cells incubated under identical conditions. The ionomycin-mediated increase in HIF-1α protein levels was sensitive to the transcription inhibitor actinomycin D and to inhibitors of calcineurin, cyclosporin A (CsA), and FK506. The increased HIF-1α protein level was paralleled by a severalfold increase in HIF-1α mRNA that could be also inhibited with actinomycin D and CsA. The HIF1A promoter activity was significantly increased in ionomycin-activated mast cells, and the promoter activity could be inhibited by CsA and FK506. Furthermore, in situ mutagenesis experiments showed that the ionomycin-mediated HIF1A promoter activity depends on a conservative NFAT-binding site. Thus, accumulation of HIF-1α in activated mast cells requires up-regulation of HIF1A gene transcription and depends on the calcineurin-NFAT signaling pathway.

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Section: Ast Cells Are Hemopoietic Cells That Reside In a Varietymentioning

confidence: 99%

HIF-1α Is Up-Regulated in Activated Mast Cells by a Process That Involves Calcineurin and NFAT

Walczak‐Drzewiecka

Ratajewski

Wagner

et al. 2008

The Journal of Immunology

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“…New investigations are finding that skin mast cells modulate the inflammatory response in healing wounds [6], play a role in neoangiogenesis [7], and may participate in tissue remodeling in the late phase of wound healing [8]. Recent evidence has revealed that skin mast cells and mast cell chymase are important for the formation of granulation tissue and the synthesis of collagen fibers that occur at the edge of the wound in the burnhealing model in mice [9].…”

Section: Introductionmentioning

confidence: 99%

Effects of low-level laser therapy on mast cell number and degranulation

Bayat

Vasheghani²,

Razavie³

et al. 2008

JRRD

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Abstract-Mast cells have been shown to participate in the wound healing process. We investigated the effects of low-level laser therapy (LLLT) on mast cell number in the inflammation, proliferation, and remodeling phases of the wound healing process of experimental burns. Sixty rats subjected to third-degree burns were divided into four groups: two laser-treated, one control, and one nitrofurazone-treated group. In the two lasertreated groups, burned areas received LLLT with a helium-neon laser at energy densities of 38.2 J/cm 2 and 76.4 J/cm 2 , respectively. The effects on mast cell number and degranulation were assessed 7, 16, and 30 days postburn (inflammation, proliferation, and remodeling phases of wound healing, respectively). Intact and degranulated mast cells were counted. Five rats with no burns were used for baseline studies. On day 7 in the first laser group, the total number of mast cells was significantly higher than in the other groups. On day 16 in the nitrofurazonetreated group, the total number of mast cells was significantly higher than in the control, first laser, and normal groups. LLLT on the experimental third-degree burns significantly increased the total number of mast cells during the inflammation phase of wound healing; also, topical application of 0.2% nitrofurazone ointment on the same burns significantly increased the total number of mast cells during the proliferation phase of burn healing.

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“…Murine skin burn wounds show a rapid increase in mast cell density and chymase activity at the wound edges in the second half of the reepithelializing period (9). Full-thickness skin wounds in mast cell-deficient mice showed normal healing rates but abnormal collagen organization at the wound edges where the preponderance of wound mast cells were found in the late stages of normal healing (49).…”

Section: Discussionmentioning

confidence: 99%

“…Chymase has several actions that could be involved in both normal and pathological wound healing such as angiotensin II formation (4), degradation of extracellular matrix (5), and activation of matrix metalloproteinases (6) and cytokines, including TGF-␤1 (7) and antibacterial peptides (8). The presence of mast cell chymase has been noted in skin wounds (9), although it is not clear that the enzyme can diffuse to the zone of reepithelialization (10). A few studies have reported non-mast cell sources of chymase.…”

mentioning

confidence: 99%

Mechanical Induction of an Epithelial Cell Chymase Associated with Wound Edge Migration

Firth

Uitto

Putnins

2008

Journal of Biological Chemistry

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Chymase is a chymotrypsin-like serine protease predominantly produced by mast cells. In this study, human cutaneous and gingival keratinocytes, ovary surface epithelia, and a porcine epithelial cell line were assayed by homology-based cloning, and the amplified DNA fragment was identified as a chymase. In vitro, chymase could not be induced by serum or cytokine treatment alone. Chymase was activated 3-fold within 60 min in basal media by scratch wounding cultured monolayers and further potentiated over 10-fold at 18 h by additional serum and cytokine treatment. Chymase activity was cell-associated and found to peak within 24 h of wounding and then steadily decreased as cultures healed, reaching baseline levels before confluence was reestablished. Affinity column purified enzyme effectively degraded fibronectin and was found by Western blot analysis using a human chymase antibody to be of about 30 kDa. Immunostaining revealed chymase activation at the wound edge colocalizing with reactive oxygen species generation. Specifically, chymase activation was attenuated by inhibition of nitric oxide, superoxide, and peroxynitrite. Exogenous peroxynitrite but not hydrogen peroxide also resulted in chymase activation in unwounded monolayers. Disruption of cytoskeletal stress fibers by cytochalasin D attenuated both wound-activated chymase and reactive oxygen species generation. Chymase inhibitor chymostatin reduced the loss of cellcell contacts and the onset of porcine and human skin epithelial cell migration at the wound edge. This shows that an epithelial chymase is rapidly activated by a ligand-independent mechanism following mechanical stress via cytoskeletal and reactive oxygen species signaling and is associated with the onset of epithelial cell migration.Chymase is a chymotrypsin-like serine protease, predominantly found in mast cells where it is stored within secretory granules as a zymogen complexed with heparin proteoglycan. It can be activated and released into the interstitial tissues following mechanical wounding such as vascular injury caused by balloon catheterization or vein grafting (1). Mast cell activation and subsequent degranulation can be induced by both liganddependent and -independent pathways. The ligand-dependent pathway operates through activation of the high affinity IgE receptor (Fc⑀RI) on the cell surface by IgE antigen triggering a cascade of signal transduction pathways (2). The ligand-independent pathway involves, at least in part, the generation of ROS, 2 including H 2 O 2 and O 2 . . Conversely, chemical scavengers of peroxides and peroxynitrites almost completely abrogate ligand-independent mast cell activation. Also, treatment of mast cells with DPI, an inhibitor of NAD(P)H oxidase production of O 2 . , greatly reduced mast cell activation (3). Chymase has several actions that could be involved in both normal and pathological wound healing such as angiotensin II formation (4), degradation of extracellular matrix (5), and activation of matrix metalloproteinases (6) and cytokines, includi...

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Skin mast cell promotion of matrix remodeling in burn wound healing in mice: relevance of chymase

Cited by 70 publications

References 33 publications

HIF-1α Is Up-Regulated in Activated Mast Cells by a Process That Involves Calcineurin and NFAT

HIF-1α Is Up-Regulated in Activated Mast Cells by a Process That Involves Calcineurin and NFAT

Effects of low-level laser therapy on mast cell number and degranulation

Mechanical Induction of an Epithelial Cell Chymase Associated with Wound Edge Migration

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