Abstract
The role of factor XIII subunit A (FXIII-A) is not restricted to hemostasis. FXIII-A is also present intracellularly in several human cells and serves as a diagnostic marker in a wide range of dermatological diseases from inflammatory conditions to malignancies. In this review, we provide a guide on the still controversial interpretation of dermal cell types expressing FXIII-A and assess the previously described mechanisms behind their accumulation under physiological and pathological conditions of the human skin. We summarize the intracellular functions of FXIII-A as well as its possible sources in the extracellular space of the dermis with a focus on its relevance to skin homeostasis and disease pathogenesis. Finally, the potential role of FXIII-A in wound healing, as a field with long-term therapeutic implications, is also discussed.
Highlights
Factor XIII (FXIII), fibrin stabilizing factor, is an enzyme consisting of two subunits: an A (FXIII-A) and a B subunit (FXIII-B) that can form a tetrameric complex in the plasma with two of each subunit (FXIII-A2B2)
In this review, besides giving a general overview on factor XIII subunit A (FXIII-A) production and its presence in the intracellular and extracellular space, we aim to summarize our current knowledge on the role of FXIII-A in thephysiology of the skin and discuss its possible cutaneous therapeutic applications. (List of abbreviations of certain forms of factor XIII used in the article is shown in Abbreviations.)
Studies by Griffin et al, using a model where mice floxed in coding exon 7 of the FXIII-A gene (F13A1) were crossed with mice transgenic for Pf4-Cre-recombinase or Cd11b-Cre-recombinase, raised the possibility that a unique Pf4-dependent progenitor cell is the major source of the plasma pool, which was independent of thrombopoietin receptor
Summary
Factor XIII (FXIII), fibrin stabilizing factor, is an enzyme consisting of two subunits: an A (FXIII-A) and a B subunit (FXIII-B) that can form a tetrameric complex in the plasma (pFXIII-A) with two of each subunit (FXIII-A2B2). As a member of the transglutaminase family, FXIII crosslinks fibrin residues to produce the mature clot in blood coagulation [1]. In addition to being a pivotal member of the coagulation cascade, FXIII-A is found intracellularly (cFXIII-A) in various cells all around the body. Monocytes [2], macrophages [3], dendritic cells (DCs) [4], fibroblasts [5], mast cells [6], and sebocytes [7], all with an important role in the homeostasis of the skin, have been listed as FXIII-A-producing cells. In this review, besides giving a general overview on FXIII-A production and its presence in the intracellular and extracellular space, we aim to summarize our current knowledge on the role of FXIII-A in the (patho)physiology of the skin and discuss its possible cutaneous therapeutic applications. (List of abbreviations of certain forms of factor XIII used in the article is shown in Abbreviations.)
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