Fibrin Is a Many Splendored Thing

Clark, Richard A.F.

doi:10.1046/j.1523-1747.2003.12575.x

Cited by 68 publications

(50 citation statements)

References 25 publications

(25 reference statements)

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“…The electron-dense contrasted matrix identified ultrastructurally as fibrin Ross and Odland 1968) is actually composed of many different components (Clark 2001(Clark ,2003. The fact that there is no receptor identified on keratinocytes for fibrin (Clark 2003;Geer and Andreadis 2003) does not prevent the cells from forming hemidesmosomal adhesions to an intermediary component associated with the fibrin rich network, possibly plasmin-mediated fibrin degradation (Geer and Andreadis 2003) and newly deposited LM-3A32 (Nguyen et al 2000b). The presence of anchoring filaments, LM-3A32, keratin concentrations and colocalization of b4 with BP230 at the adhesion sites identifies these structures as hemidesmosomes (Ishiko et al 1998).…”

Section: Discussionmentioning

confidence: 99%

Ultrastructural Localization of Integrin Subunits β4 and α3 Within the Migrating Epithelial Tongue of In Vivo Human Wounds

Underwood

Carter

Usui

et al. 2008

J Histochem Cytochem.

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Subsequent to wounding, keratinocytes must quickly restore barrier function. In vitro wound models have served to elucidate mechanisms of epithelial closure and key roles for integrins α6β4 and α3β1. To extrapolate in vitro data to in vivo human tissues, we used ultrathin cryomicrotomy to simultaneously observe tissue ultrastructure and immuno-gold localization in unwounded skin and acute human cutaneous wounds. Localization of the β4 integrin subunit in unwounded skin shows dominant hemidesmosomal association and minor basal keratinocyte lateral filopodic cell–cell expression. After wounding, β4 dominantly localized to cytokeratin-rich regions (trailing edge hemidesmosomes) and minor association with lamellipodia (leading edge). β4 colocalizes with α3 within filopodia juxtaposed to wound matrix, and increased concentrations of β4 were found in cytoplasmic vesicles within basal keratinocytes of the migrating tongue. α3 integrin subunit dominantly localized to filopodia within basal keratinocyte lateral cell–cell interfaces in unwounded skin and both cell–cell and cell–matrix filopodic interactions in wounded skin. This study indicates that β4 interacts with the extracellular environment through both stable and transient interactions and may be managed through a different endosomal trafficking pathway than α3. α3 integrin, despite its ability to respond to alternate ligands after wounding, does so through a single structure, the filopodia.

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Section: Discussionmentioning

confidence: 99%

Ultrastructural Localization of Integrin Subunits β4 and α3 Within the Migrating Epithelial Tongue of In Vivo Human Wounds

Underwood

Carter

Usui

et al. 2008

J Histochem Cytochem.

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“…As well as providing essential hemostasis and support for cell migration, the fibrin matrix is thought to play a much broader physiological role during the repair process. 1,2 For instance, fibrin(ogen) is centrally involved in platelet aggregation and activation, its cleavage fragments have been identified as key molecular effectors of the fibroproliferative response and it acts as a storage reservoir for a number of important growth factors, proteases, and their inhibitors. During the repair process, the fibrin-rich matrix is degraded and replaced by a more permanent fibrous matrix predominately composed of collagen.…”

mentioning

confidence: 99%

Fibrin-Induced Skin Fibrosis in Mice Deficient in Tissue Plasminogen Activator

Giorgio-Miller

Bottoms

Laurent

et al. 2005

The American Journal of Pathology

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The deposition of fibrin is an integral part of the tissue repair process, but its persistence is also associated with a number of fibrotic conditions. This study addressed the hypothesis that reduced fibrinolysis and fibrin persistence are associated with an enhanced accumulation of collagen and the development of skin fibrosis. Decreased fibrinolysis was confirmed in fibrin gel cultures that contained human dermal fibroblasts plus the specific plasmin inhibitor ␣ 2 -antiplasmin or dermal fibroblasts isolated from plasminogen activator (PA)-deficient mice. Collagen accumulation was significantly increased in the presence of inhibitor and in tPA-deficient, but not uPAdeficient, fibroblasts compared with controls. These findings were also confirmed using a skin fibrosis model in which multiple injections of fibrin were given subcutaneously to PA-deficient mice. Injection sites from tPA-deficient mice displayed significantly increased collagen levels compared with uPA-deficient mice and wild-type controls. Up-regulation of fibroblast procollagen gene expression and reduced activation of pro-MMP-1 appeared to mediate the increase in collagen by human dermal fibroblasts in the presence of ␣2-antiplasmin. These findings suggest that persistent fibrin is associated with enhanced collagen accumulation that may result in the development of fibrotic skin disorders in which reduced fibrinolysis is a feature.

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“…This results in the formation of a loosely assembled clot, subsequently stabilized by covalent cross-links created by plasma transglutaminase (factor XIIIa). This stable clot not only plays a haemostatic role, but also serves as an initial scaffold for tissue regeneration, serving as a platform for cell migration and proliferation [90][91][92][93][94][95][96].…”

Section: Fibrinogenmentioning

confidence: 99%

The Use of Natural Polymers in Tissue Engineering: A Focus on Electrospun Extracellular Matrix Analogues

et al. 2010

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Natural polymers such as collagens, elastin, and fibrinogen make up much of the body's native extracellular matrix (ECM). This ECM provides structure and mechanical integrity to tissues, as well as communicating with the cellular components it supports to help facilitate and regulate daily cellular processes and wound healing. An ideal tissue engineering scaffold would not only replicate the structure of this ECM, but would also replicate the many functions that the ECM performs. In the past decade, the process of electrospinning has proven effective in creating non-woven ECM analogue scaffolds of micro to nanoscale diameter fibers from an array of synthetic and natural polymers. The ability of this fabrication technique to utilize the aforementioned natural polymers to create tissue engineering scaffolds has yielded promising results, both in vitro and in vivo, due in part to the enhanced bioactivity afforded by materials normally found within the human body. This review will present the process of electrospinning and describe the use of natural polymers in the creation of bioactive ECM analogues in tissue engineering.

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Fibrin Is a Many Splendored Thing

Cited by 68 publications

References 25 publications

Ultrastructural Localization of Integrin Subunits β4 and α3 Within the Migrating Epithelial Tongue of In Vivo Human Wounds

Ultrastructural Localization of Integrin Subunits β4 and α3 Within the Migrating Epithelial Tongue of In Vivo Human Wounds

Fibrin-Induced Skin Fibrosis in Mice Deficient in Tissue Plasminogen Activator

The Use of Natural Polymers in Tissue Engineering: A Focus on Electrospun Extracellular Matrix Analogues

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